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INVEGA SUSTENNA® (paliperidone palmitate)

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Adverse Event of INVEGA SUSTENNA - Weight Change

Last Updated: 01/17/2025

Summary

Atypical antipsychotic drugs, including INVEGA SUSTENNA, have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.¹ Clinical monitoring of weight is recommended.²
In the short-term pivotal trials, the proportion of patients with a ≥7% increase in baseline body weight was 4-13% for INVEGA SUSTENNA (with a dose related trend) versus 2-5% for placebo.³^-⁶ The mean change in weight from baseline to endpoint ranged from 0.4 to 4.5 kg for INVEGA SUSTENNA versus -0.2 to -0.7 for placebo.³^-⁷
In a long-term open-label pharmacokinetic and safety study in schizophrenia in which the highest dose available (234 mg) was evaluated, 27% of patients had increases of ≥7% in body weight from baseline to endpoint during the study. Mean change in body weight from open-label baseline to endpoint was 4.2 kg in patients who completed the study at 234 mg and 0.6 kg in those who did not complete the study at 234 mg.⁸
In a 24-month, randomized, rater-blinded, prospective, open-label, international study (PROSIPAL) in patients with schizophrenia, the mean change in weight from baseline to last-observation-carried-forward (LOCF) endpoint was 2.3 kg and 1.9 kg for patients receiving INVEGA SUSTENNA versus oral antipsychotics, respectively.⁹
In a 15-month, prospective, randomized, open-label, event monitoring board (EMB)-blinded, multicenter US study (PRIDE: Paliperidone Palmitate Research In Demonstrating Effectiveness) designed to reflect real-world schizophrenia patients, treatments and outcomes, a weight gain increase ≥7% was observed in 32.4% of INVEGA SUSTENNA and 14.4% of oral antipsychotic patients.¹⁰
In a long-term, double-blind, noninferiority study, a similar percentage of patients in both arms (paliperidone palmitate 3-month (PP3M): 15%; INVEGA SUSTENNA: 16%) experienced a ≥7% increase in weight from double-blind baseline to endpoint.¹¹
At the 15-month double-blind endpoint of the schizoaffective study, INVEGA SUSTENNA was associated with a mean change in weight of -0.2 kg and 13.0% of subjects had an increase in body weight of ≥7% (n=164); the placebo group had a mean change in weight of -0.8 kg and 6.0% of subjects had an increase in body weight of ≥7% (n=170).¹²

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to mg of paliperidone palmitate to reflect the commercially available dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

INVEGA SUSTENNA doses expressed as 25, 50, 75, 100, and 150 mg eq. are equal to 39, 78, 117, 156, and 234 mg of paliperidone palmitate, respectively.

BACKGROUND

The use of second-generation antipsychotics (SGAs) has been associated with weight gain and metabolic abnormalities, which place patients at increased cardiovascular risk.¹³ Changes in body composition and weight gain may be contributing factors to the metabolic abnormalities observed in these patients. Because there are limited data in drug-naïve patients, it is unclear whether weight gain is due to the drug treatment or to the psychiatric disease itself. The prevalence of obesity in patients with schizophrenia has been estimated to be approximately 1.5- to 2-fold higher than the prevalence in the general population; however, lifestyle characteristics such as sedentary behavior may contribute to the higher prevalence of weight gain.²^,¹³ The mechanism of SGA-associated weight gain is unknown; however, altered binding affinities for serotonin, norepinephrine, dopamine, and histamine-H1 receptors may be implicated through alterations in appetite and satiety.¹³ Rapid weight gain may be observed over the first 2 to 3 months of treatment with an SGA (approximately 0.5 to 5.0 kg over 10 weeks); however, weight gain may extend past a year of treatment.¹³ The risk of weight gain with each antipsychotic medication should be a factor in treatment selection for patients with body mass index (BMI) values of ≥25.² Weight and BMI measurements should be checked routinely (at every visit or approximately every 4 weeks), especially for the first 3 to 6 months after treatment initiation or change in therapy and every 3 months thereafter.²^,¹³ For patients with BMI values ≥18.5, 1-unit increases in BMI indicate a need for intervention (closer monitoring of weight, participation in weight management program, use of weight loss therapies, or change in antipsychotic regimen).²

SCHIZOPHRENIA and SCHIZOAFFECTIVE CLINICAL STUDIES

Schizophrenia and Schizoaffective Clinical Trial Data

Trial Design	Mean Weight Change
SCHIZOPHRENIA
Double-Blind Trials including Open-Label Extensions
Hough (2010)¹⁴ conducted a longer-term, DB, randomized, multicenter, PBO-controlled, parallel group study examining the efficacy and safety of INVEGA SUSTENNA in delaying time-to-relapse in schizophrenic patients following an initial 9-week, OL transition phase and 24-week, OL maintenance phase (n=849, transition and maintenance population; n=408, DB safety analysis set). Dosing Schedule (All doses administered IM via gluteal muscle): 9-week OL transition phase INVEGA SUSTENNA 78 mg on day 1 and day 8 followed by adjustable INVEGA SUSTENNA doses (39, 78, or 156 mg) administered every 4 weeks for the rest of the transition period. 24-week OL maintenance phase Adjustable INVEGA SUSTENNA doses (39, 78, or 156 mg) administered every 4 weeks for the first 12 weeks followed by fixed INVEGA SUSTENNA doses of 39, 78, or 156 mg. every 4 weeks for the last 12 weeks. DB phase Fixed INVEGA SUSTENNA doses of 39, 78, or 156 mg (n=205) or PBO (n=203) every 4 weeks.	Mean change in body weight from transition baseline to DB endpoint: INVEGA SUSTENNA: 1.9 kg; PBO: 0 kg Patients with ≥7% increase in body weight from transition baseline to DB endpoint: INVEGA SUSTENNA: 23%; PBO: 12% Patients with ≥7% increase in body weight during DB phase: INVEGA SUSTENNA: 6%; PBO: 3% At the end of the DB phase, treatment-emergent increases in weight were observed in 7% of INVEGA SUSTENNA patients and 1% of PBO patients.
Gopal (2011)¹⁵; Alphs (2009) ¹⁶ conducted a 52-week, OLE study assessing the long-term safety and efficacy of INVEGA SUSTENNA in 388 patients with schizophrenia following a Phase 3, DB, randomized, multicenter, PBO-controlled, parallel group trial (Hough 2010).¹⁴ Study Treatment All patients received gluteal injections of INVEGA SUSTENNA beginning with a 78 mg doses followed by flexible dosing (39, 78, 117, or 156 mg) once every 4 weeks for 12 injections. Oral supplementation with paliperidone extended-release was permitted for all patients for the first 8 OLE weeks in order to avoid treatment interruption (initiated at 6 mg/day; titrated up/down in 3 mg/day increments within a range of 3-12 mg/day). Study Groups PBO/INVEGA SUSTENNA (n=153): PBO during DB phase; INVEGA SUSTENNA during OLE phase. INVEGA SUSTENNA/INVEGA SUSTENNA (n=161): INVEGA SUSTENNA during DB and OLE phases. No DB/INVEGA SUSTENNA (n=74): Patients in transition or maintenance phases entering directly to OLE phase upon DB termination.	Mean change from OL baseline to endpoint: Body weight: 0.9 kg BMI: 0.3 kg/m² From OL baseline to endpoint, a ≥7% increase in weight was observed in 13% of patients (n=47) with the lowest incidence observed in the INVEGA SUSTENNA/INVEGA SUSTENNA group. The following percentages of patients experienced treatment-emergent increases in weight: PBO/INVEGA SUSTENNA: 7% (n=11/150) INVEGA SUSTENNA/INVEGA SUSTENNA: 4% (n=7/161) No DB/INVEGA SUSTENNA: 9% (n=7/74) One patient discontinued treatment during the extension due to weight gain/increased appetite
Sliwa (2014)¹⁷ conducted a post hoc analysis of Hough (2010)¹⁴ and Gopal (2011)¹⁵ evaluating the long-term effects of INVEGA SUSTENNA on metabolic AEs; patients were grouped according to BMI (underweight, <19 kg/m², n=29; normal, 19-24 kg/m², n=229; overweight, 25-29 kg/m², n=232; obese, ≥30 kg/m², n=154) Includes only those patients treated with INVEGA SUSTENNA continuously from study entry through discontinuation or study completion.	Most commonly (≥2%) occurring metabolic TEAEs included: Weight gain: Underweight: 0%; Normal: 11.4%; Overweight: 7.3%; Obese: 11.7% Change in mean weight and BMI category (TR baseline to DB endpoint, median duration 156 days) Normal-weight (2.4 kg; P<0.001) and overweight (1.68 kg; P=0.008) groups significantly gained weight from TR baseline to DB endpoint. A ≥7% increase in weight was observed in 5% of patients in the normal-weight and obese groups and 8% of patients in the overweight group. Percentage of patients shifting towards a higher BMI category: underweight (60% [3/5]); normal-weight (18% [13/71]); overweight (9% [6/70]) Percentage of patients shifting towards a lower BMI category: overweight (7% [5/70]); obese (9% [5/54]) Change in mean weight and BMI category (TR baseline to OLE endpoint, median duration 204 days) With the exception of the obese group, significant increases in mean weight were observed for the underweight (3.82 kg; P=0.045), normal-weight (3.48 kg; P<0.001) and overweight (1.62 kg; P=0.003) groups. A weight increase of ≥7% was observed in 15%, 6% and 4% of patients in the normal-weight, obese and overweight groups, respectively. Patients shifting towards a higher BMI category: underweight (67% [6/9]); normal-weight (28% [25/89]); overweight (16% [11/70]) Patients shifting towards a lower BMI category: overweight (9% [8/84]); obese (19% [8/43])
Pandina (2011)¹⁸ conducted a 13-week, randomized, DB, double-dummy, active-controlled, parallel-group, multicenter study assessing non-inferiority of INVEGA SUSTENNA to RLAI in the treatment of patients with schizophrenia (n=1214, safety analysis set). INVEGA SUSTENNA (n=606): Deltoid inj of INVEGA SUSTENNA 234 mg on day 1 followed by a 156-mg deltoid inj on day 8; thereafter, patients received flexibly dosed INVEGA SUSTENNA injections on days 36 (78 or 156 mg) and 64 (78, 156, or 234 mg) in either the deltoid or gluteal muscle. RLAI (n=608): RLAI 25 mg on days 8 and 22, followed by 25 or 37.5 mg on days 36 and 50; thereafter, patients received flexible doses of 25, 37.5, or 50 mg on days 64 and 78, all in the gluteal muscle. Oral supplementation with RIS (1-6 mg) was administered for the first 28 days. Optional supplementation with RIS was permitted under certain circumstances outlined in the protocol.	Mean change in body weight from baseline to endpoint: INVEGA SUSTENNA: 1.1 kg RLAI: 1.0 kg
Gopal (2010)⁶ conducted a 13-week, multicenter, randomized, DB, PBO-controlled, dose-response study evaluating the efficacy and safety of 3 fixed doses of INVEGA SUSTENNA (78, 156, or 234 mg), administered via gluteal inj on days 1, 8, 36 and 64, in patients with schizophrenia (n=388, safety analysis set).	Baseline to Endpoint - Mean Change in Body Weight and Percentage of Patients with ≥7% Increase in Body Weight: INVEGA SUSTENNA 78 mg: 1.0 kg; 12% INVEGA SUSTENNA 156 mg: 1.5 kg; 10% INVEGA SUSTENNA 234 mg: 0.9 kg: 4% PBO: -0.7 kg; 2%
Kramer (2010)⁵ conducted a 9-week, DB, randomized, international study comparing the safety and efficacy between INVEGA SUSTENNA (two fixed doses) and PBO in the treatment of adults with schizophrenia (n=247). Following a 5-day screening/washout phase and a 7-day oral run-in period, patients were randomized to receive gluteal IM injections of INVEGA SUSTENNA 78 mg (n=79), INVEGA SUSTENNA 156 mg (n=84), or PBO (n=84), without oral supplementation, on days 1, 8, and 36.	Mean change in body weight and BMI from baseline to endpoint: (P-value vs PBO) INVEGA SUSTENNA 156 mg: 1.4 kg (P≤0.001); 0.5 kg/m² (P≤0.001) INVEGA SUSTENNA 78 mg: 0.7 kg (P=0.059); 0.3 kg/m² (P=0.036) PBO: -0.3 kg; -0.1 kg/m2 Patients with ≥7% increase in body weight from baseline to endpoint: INVEGA SUSTENNA 156 mg: 6%; INVEGA SUSTENNA 78 mg: 8%; PBO: 4% TEAEs of weight increased: 1% with PBO and 3% with INVEGA SUSTENNA 78 mg
Pandina (2010)³; Haskins (2009)⁴ 13-week, phase 3, randomized, DB, PBO-controlled, international dose response INVEGA SUSTENNA study conducted in patients experiencing an acute exacerbation of established schizophrenia (n=652). Initiation Dose: Day 1 (Deltoid IM Inj) INVEGA SUSTENNA 234 mg (n=488) PBO (n=164) Fixed Dose: Day 8, 36, and 64 (Deltoid or Gluteal IM Inj) 1)INVEGA SUSTENNA 234 mg (n=163) 2)INVEGA SUSTENNA 156 mg (n=165) 3)INVEGA SUSTENNA 39 mg (n=160) 4)PBO (n=164)	Mean change in body weight from baseline to endpoint: INVEGA SUSTENNA 39 mg: 0.4 kg; INVEGA SUSTENNA 156 mg: 0.7 kg; INVEGA SUSTENNA 234 mg: 1.4 kg; PBO: -0.2 kg Weight gain increase of ≥7% from baseline to endpoint: INVEGA SUSTENNA 39 mg: 6%; INVEGA SUSTENNA 156 mg: 8%; INVEGA SUSTENNA 234 mg: 13%; PBO: 5% All adverse event reports of increase in weight occurred during treatment days 1-7: 1 (0.6%) with PBO and 2 (0.4%) with INVEGA SUSTENNA
Nasrallah (2010)⁷ conducted a 13-week, phase 3, multicenter, randomized, DB, PBO-controlled, parallel group, international dose-response study evaluating the efficacy and safety of 3 fixed doses of INVEGA SUSTENNA (39, 78, or 156 mg), administered by gluteal IM inj on days 1, 8, 36, and 64, in patients with schizophrenia (n=517, safety analysis set).	Treatment-emergent increases in weight occurred in 4% of the INVEGA SUSTENNA patients and in 0% of the PBO patients. Mean increases from baseline to endpoint in weight and BMI appeared to be dose related for the INVEGA SUSTENNA groups. Mean increases from baseline to endpoint in weight and BMI: INVEGA SUSTENNA 156 mg: 1.3 kg and 0.5 kg/m², respectively INVEGA SUSTENNA 78 mg: 0.8 kg and 0.3 kg/m², respectively INVEGA SUSTENNA 39 mg: 0.4 kg and 0.2 kg/m², respectively PBO patients experienced mean decreases in weight (-0.5 kg) and BMI (-0.1 kg/m²) from baseline to endpoint.
Hough (2009)¹⁹ conducted a 25-week, randomized, DB, multicenter, cross-over study assessing the safety and tolerability of INVEGA SUSTENNA administered via a deltoid or gluteal IM inj in adults with stable schizophrenia (n=252, safety analysis set). Patients were randomized to receive one of two inj-site sequences (Period 1: Doses administered on days 1, 8, 36, and 64 followed by Period 2: Doses administered on days 92, 120, and 148). 1) GD (Gluteal IM inj during period 1 followed by Deltoid IM inj during period 2) 2) DG (Deltoid IM inj during period 1 followed by Gluteal IM inj during period 2)	INVEGA SUSTENNA doses: 78 mg: GD (n=40); DG (n=42) 117 mg: GD (n=44); DG (n=40) 156 mg: GD (n=40); DG (n=46) During period 2, treatment-emergent increases in weight occurred in 7% of patients after deltoid administration. Mean change in weight from baseline: INVEGA SUSTENNA 117 mg: 2.6 kg Other dose groups: from -1.0 kg to 0.5 kg
Additional Double-Blind Trials
Savitz et al (2016)¹¹ conducted a randomized, DB, parallel-group, multicenter, noninferiority study of PP3M and INVEGA SUSTENNA. The study consisted of 4 phases: a 3-week screening phase, a 17-week, OL stabilization phase, a 48-week DB phase, and a follow-up phase. During the OL phase, 1429 patients received INVEGA SUSTENNA in the following doses: 234 mg on day 1 (*deltoid* IM); 156 mg on day 8 (*deltoid* IM); flexible doses of 78-234 mg (*deltoid or gluteal* IM) at weeks 5, 9 and 13. Patients in the DB phase received fixed doses of INVEGA SUSTENNA (78, 117, 156 or 234 mg; n=512) or a 3.5 multiple of PP3M (273, 410, 546, 819 mg; n=504) in the deltoid or gluteal muscle.	The mean duration of exposure was 295.1 days for PP3M at a mean dose of 647.01 mg and 286.7 days for INVEGA SUSTENNA at a mean dose of 185.8 mg. During the OL maintenance phase, increased weight (5%) was among the most frequently reported (≥2%) TEAEs. The same percentage of patients (21%) in each arm reported increased weight during the DB phase. A decrease in weight was reported by 3% of patients in each arm. From OL baseline to DB endpoint, the mean increase in body weight was 2.19 kg and 3.07 kg in the PP3M (n=495) and INVEGA SUSTENNA (n=495) groups, respectively. In the PP3M group, 136 (27%) patients had a ≥7% increase in body weight as compared to 150 (30%) patients in the INVEGA SUSTENNA group. From DB baseline to endpoint, a similar percentage of patients in both arms (PP3M: 15%, n=75; INVEGA SUSTENNA: 16%, n=81) experienced a ≥7% increase in weight. Overall, 37 (7%) of PP3M-treated patients and 21 (4%) of INVEGA SUSTENNA-treated patients had a ≥7% decrease in body weight.
McEvoy et al (2014)²⁰ conducted the ACLAIMS trial, a DB, randomized, multisite, parallel-group US clinical trial comparing the effectiveness of INVEGA SUSTENNA versus HAL decanoate for the maintenance treatment of schizophrenia or schizoaffective disorder. Long-acting injectable treatment (≤24 months): INVEGA SUSTENNA (n=147): Initiation doses, IM deltoid (234 mg on day 1; 156 mg on day 8); Maintenance doses, IM deltoid or gluteal (117 mg monthly) HAL decanoate (n=147): Initiation doses, IM deltoid (50 mg on day 1; 50 mg on day 8); Maintenance doses, IM deltoid or gluteal (75 mg on days 28 and 56, then 50 mg monthly) Mean monthly doses of INVEGA SUSTENNA and HAL decanoate ranged from 129-169 mg and 67-83 mg, respectively. Patients were followed for a median of 488 days	Significant treatment group differences were observed with regard to weight gain (P<0.0001). At month 6, the least-squares mean weight change increased for the INVEGA SUSTENNA group (2.17 kg; 95% CI, 1.25,3.09) and decreased for the HAL decanoate group (-0.96; 95% CI, -1.88, -0.04). Discontinuation due to weight gain: INVEGA SUSTENNA (4.8%); HAL decanoate (1.4%)
Takahashi et al (2013)²¹ conducted a 13-week, randomized, DB, PBO-controlled trial assessing the safety and efficacy of INVEGA SUSTENNA in Asian patients with schizophrenia (N=323; mean age: 45 years; 57% male). *INVEGA SUSTENNA*, n=159: 234 mg on day 1 (deltoid IM); 156 mg on day 8 (deltoid IM); once-monthly injections of 117 mg (deltoid IM or gluteal IM) on days 36 and 64. *PBO*, n=164 Mean duration of INVEGA SUSTENNA and PBO exposure was 87 and 50 days, respectively.	There were no clinically relevant changes in weight, waist circumference or BMI for either treatment group. However, more patients in the INVEGA SUSTENNA versus PBO group experienced a ≥7% increase in weight (9.4% versus 2.4%, respectively). TEAEs (≥2% any treatment group) included: Weight increased: INVEGA SUSTENNA (4.4%); PBO (0%) Decreased appetite: INVEGA SUSTENNA (3.1%); PBO (3.7%) Weight decreased: INVEGA SUSTENNA (1.9%); PBO (4.3%)
Fleischhacker (2012)²² conducted a 53-week, randomized, DB, active-controlled, parallel-group, multicenter, comparative study designed to assess the non-inferiority of INVEGA SUSTENNA to RLAI (n=747, safety analysis set). INVEGA SUSTENNA + Oral PBO: Flexibly dosed INVEGA SUSTENNA (39, 78, 117, or 156 mg) + oral PBO supplementation every 4 weeks following an initiation dose of INVEGA SUSTENNA 78 mg administered on days 1 and 8. All IM doses administered via gluteal muscle. RLAI + Oral RIS: Flexibly dosed oral RIS (1-6 mg/day) was administered for 4 weeks initially and for 3 weeks following each RLAI dosage increase. Patients received a PBO inj on day 1, RLAI 25 mg on days 8 and 22 and flexibly dosed RLAI (25, 37.5, or 50 mg) administered via gluteal muscle every 2 weeks thereafter.	The mean change in body weight, from baseline to endpoint, was -0.2 kg for the INVEGA SUSTENNA + PBO group and 0.8 kg for the RLAI + RIS group. Weight gain increase of ≥7% from baseline to endpoint: INVEGA SUSTENNA + PBO: 14% RLAI + RIS: 15%
Rater-Blinded Studies (≥12 Months)
Alphs et al (2015)¹⁰ conducted a 15-month, prospective, randomized, OL, event monitoring board (EMB)-blinded, multicenter US study (PRIDE: Paliperidone Palmitate Research In Demonstrating Effectiveness) designed to reflect real-world schizophrenia patients, treatments and outcomes. The clinician and patient reviewed the list of available OAPs (ARI, HAL, OLA, PALI, PER, QUE and RIS) before randomization and could preselect up to 6 from the list based on prior experience. Patients were stratified on the basis of their selection of OAP treatments and randomly assigned to flexibly dosed INVEGA SUSTENNA (78-234 mg) or flexibly dosed OAP therapy.	The most frequently reported (>10% of patients in either group) TEAEs for the INVEGA SUSTENNA and OAP groups, respectively included: weight gain (11.9%; 6%) Weight gain increase ≥7% was observed in 32.4% of INVEGA SUSTENNA and 14.4% of OAP patients.
Schreiner et al (2015)⁹ conducted a 24-month, randomized, rater-blinded, prospective, OL, international study (PROSIPAL) comparing treatment outcomes, including time to relapse, among patients receiving OAPs versus INVEGA SUSTENNA. Mean modal doses of individual APs: INVEGA SUSTENNA (n=352)^a: 158.7 mg; ARI (n=81): 19.1 mg; HAL (n=34): 8.2 mg; OLA (n=49): 12.9 mg; PALI (n=77): 7.5 mg; QUE (n=65): 489.2 mg; RIS (n=57): 4.3 mg	Results and demographics are reported for the core intent-to-treat (ITT) population (acute phase responders who received at least one dose of study medication and had at least one post-baseline efficacy or safety assessment during the core treatment phase) TEAEs affecting ≥5% of patients in any group included: weight increase (INVEGA SUSTENNA: 15.9%; OAPs: 17.4%) Mean change in weight from baseline to LOCF endpoint: INVEGA SUSTENNA (2.3 kg); OAPs (1.9 kg) Proportion of patients experiencing ≥7% increase in body weight from baseline to LOCF endpoint: OLA (37.5%); RIS (26.8%); ARI (23.5%); INVEGA SUSTENNA (20.6%); PAL (19.7%); QUE (15.4%); HAL (11.8%)
Pooled Analysis of the PRIDE and PROSIPAL Studies
Sajatovic et al (2024)²³ conducted a post hoc analysis to evaluate the overall risk of relapse by duration of illness (0-3 years, >3-5 years, and >5 years) in adult patients with schizophrenia who received INVEGA SUSTENNA or OAP in the PRIDE and PROSIPAL studies. A total of 1157 patients were included: 0-3 years: INVEGA SUSTENNA, n=253; OAP, n=263 >3-5 years: INVEGA SUSTENNA, n=138; OAP, n=134 >5 years: INVEGA SUSTENNA, n=187; OAP, n=182	Weight increase was one of the most common TEAEs (occurring in ≥10% of patients): 0-3 years: INVEGA SUSTENNA, 18.6% (47/253); OAP, 17.5% (46/263) >3-5 years: INVEGA SUSTENNA, 12.3% (17/138); OAP, 16.4% (22/134) >5 years: INVEGA SUSTENNA, 12.8% (24/187); OAP, 7.1% (13/182)
Open-Label Studies (≥12 Months)
Zhang et al (2015)²⁴ conducted a phase 3b, OL, multicenter study evaluating the safety, tolerability, and efficacy of INVEGA SUSTENNA in Asian/Australian patients with recent-onset schizophrenia who previously failed treatment with oral antipsychotics (n=521 ITT/safety population). Dosing: Deltoid IM inj on day 1 (234 mg) and day 8 (156 mg) followed by flexible once-monthly injections of 78-234 mg (deltoid IM or gluteal IM).	Mean duration of exposure: 382.6 days. Mean maintenance dose after day 8: 157.2 mg Most common (≥5% patients) TEAEs included: abnormal weight gain (9.8%) and weight increased (7.5%) Mean increase in body weight from baseline to endpoint (month 18): 3.91 kg (P<0.0001) A ≥7% increase in body weight was reported in 41.8% of patients from baseline to month 18.
Wakamatsu et al (2013)²⁵ conducted a 57-week, OL, flexible-dose study evaluating the long-term safety and efficacy of INVEGA SUSTENNA in Japanese patients with schizophrenia (N=201; mean age: 45.5 years; 51.7% male; n=184 in safety analysis set). Dosing: Deltoid IM inj on day 1 (234 mg) and day 8 (156 mg) followed by flexible once-monthly injections (deltoid IM or gluteal IM).	Patients received a mean INVEGA SUSTENNA dose of 166.8 mg for a mean duration of 238.7 days. Weight increase (≥7%) was reported in 17.4% of patients.
Coppola (2012)⁸ conducted a 53-week, OL, multidose, multicenter study evaluating the pharmacokinetics and long-term safety and tolerability of INVEGA SUSTENNA 234 mg in adults with stable schizophrenia (n=212, safety analysis set). Following a screening and washout phase of ≤21 days, each patient received a deltoid IM inj of INVEGA SUSTENNA 234 mg on day 1. Each patient who tolerated the dose (Group A, n=186) received a second deltoid IM inj of INVEGA SUSTENNA 234 mg on day 8 and 12 once-monthly injections (deltoid or gluteal muscle) starting on day 36. Patients who were unable to tolerate the 234-mg dose or unwilling to participate in intensive pharmacokinetic sampling (Group B, n=26) received a second IM inj of INVEGA SUSTENNA 78-234 mg (flexible dose) on day 8 (deltoid or gluteal muscle) and 12 once-monthly injections starting on day 36 (deltoid or gluteal muscle).	27% of patients had increases of ≥7% in body weight from baseline to endpoint during the study. Average body weight increased by 3.9% from baseline to endpoint. Treatment-emergent increases in weight occurred in 10.6% of patients who completed the study at 234 mg throughout (n=104) and in 7.4% of patients who did not complete the study at 234 mg (n=108). Mean change in body weight from OL baseline to endpoint was 4.2 kg in patients who completed the study at 234 mg throughout and 0.6 kg in those who did not complete the study at 234 mg. BMI followed a similar trend, with an increase of 1.5 kg/m² for patients who completed the study at 234 mg throughout and an increase of 0.3 kg/m² for those who did not complete the study at 234 mg.
SCHIZOAFFECTIVE DISORDER
Fu et al¹²^,²⁶ conducted an international, long-term, DB, PBO-controlled, randomized-withdrawal study of INVEGA SUSTENNA in patients with schizoaffective disorder. During the 15-month, DB phase, stable patients were randomized to PBO (n=170) or a fixed dose of INVEGA SUSTENNA (n=164) The INVEGA SUSTENNA dose distribution during the DB phase: 78 mg (4.9%), 117 mg (9.8%), 156 mg (47%) or 234 mg (38.4%) doses.	Most common TEAEs (≥5% INVEGA SUSTENNA or PBO) included: weight increased (8.5% versus 4.7%, respectively) One patient in the INVEGA SUSTENNA group discontinued therapy due to an increase in weight. Proportion of INVEGA SUSTENNA and PBO patients with a ≥7% increase in weight was 13% and 6%, respectively while the mean change in weight was -0.2 kg and -0.8 kg, respectively.
Abbreviations: AD, antidepressant; AP, antipsychotic; ARI, aripiprazole: BMI, body mass index; DB, double blind; FLU, fluphenazine; FPT, flupentixol; HAL, haloperidol; IM, intramuscular; Inj, injection; LAI, long-acting injectable; LOCF, last-observation-carried-forward; MS, mood stabilizer; OAP, oral antipsychotic; OL, open-label; OLA, olanzapine; OLE, open-label extension; PALI, paliperidone; PBO, placebo; PER, perphenazine; PP3M, paliperidone palmitate 3-month; QUE, quetiapine; RIS, risperidone; RLAI, risperidone long acting injection; TEAE, treatment emergent adverse event; TR, transition; ZUC, zuclopenthixol. ^aMean maintenance dose (fourth inj onwards); 91.5% (322/352) received INVEGA SUSTENNA according to appropriate study protocol dosing schedule.

Comparison to Olanzapine

In a randomized, rater-blinded, 13-week study (n=57) comparing INVEGA SUSTENNA and olanzapine in Chinese first-episode schizophrenia patients, less mean weight gain was reported with INVEGA SUSTENNA (3.64 kg) than with olanzapine (4.86 kg), although there was no significant difference between the 2 groups (P=0.553).²⁷

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 19 December 2024.

The information included in this scientific response focuses on published double-blind, rater-blinded (≥12 months) and open-label (≥12 months) studies in schizophrenia and schizoaffective disorder in adults.

References

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1	Carter NJ. Extended-release intramuscular paliperidone palmitate: a review of its use in the treatment of schizophrenia. Drugs. 2012;72(8):1137-1160.
2	Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004;161(8):1334-1349.
3	Pandina GJ, Lindenmayer JP, Lull J, et al. A randomized placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol. 2010;30(3):235-244.
4	Haskins J, Silwa JK, Ma YW, et al. Efficacy and safety of 234 mg initiation dose and 3-fixed maintenance doses of paliperidone palmitate-a once-monthly injectable atypical antipsychotic. Poster presented at: The U.S. Psychiatric and Mental Health Congress; November 2-5, 2005; Las Vegas, NV.
5	Kramer M, Litman R, Hough D, et al. Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study. Int J Neuropsychopharmacol. 2010;13(5):635-647.
6	Gopal S, Hough DW, Xu H, et al. Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study. Int Clin Psychopharmacol. 2010;25(5):247-256.
7	Nasrallah HA, Gopal S, Gassmann-Mayer C, et al. A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia. Neuropsychopharmacology. 2010;35(10):2072-2082.
8	Coppola D, Liu Y, Gopal S, et al. A one-year prospective study of the safety, tolerability and pharmacokinetics of the highest available dose of paliperidone palmitate in patients with schizophrenia. BMC Psychiatry. 2012;12:26.
9	Schreiner A, Aadamsoo K, Altamura AC, et al. Paliperidone palmitate versus oral antipsychotics in recently diagnosed schizophrenia. Schizophr Res. 2015;169(1-3):393-399.
10	Alphs L, Benson C, Cheshire-Kinney K, et al. Real-world outcomes of paliperidone palmitate compared to daily oral antipsychotic therapy in schizophrenia: a randomized, open-label, review board-blinded 15-month study. J Clin Psychiatry. 2015;76(5):554-561.
11	Savitz AJ, Xu H, Gopal S, et al. Efficacy and safety of paliperidone palmitate 3-month formulation for patients with schizophrenia: a randomized, multicenter, double-blind, noninferiority study. Int J Neuropsychopharmacol. 2016;19(7):pyw018.
12	Fu DJ, Turkoz I, Simonson RB, et al. Paliperidone palmitate once-monthly reduces risk of relapse of psychotic, depressive, and manic symptoms and maintains functioning in a double-blind, randomized study of schizoaffective disorder. J Clin Psychiatry. 2015;76(3):253-262.
13	American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601.
14	Hough D, Gopal S, Vijapurkar U, et al. Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2010;116(2-3):107-117.
15	Gopal S, Vijapurkar U, Lim P, et al. A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia. J Psychopharmacol. 2011;25(5):685-697.
16	Alphs L, Haskins J, Bossie C. Long-term metabolic outcomes with paliperidone palmitate, a once-monthly long-acting injectable antipsychotic agent, in the treatment of subjects with schizophrenia. Poster presented at: American College Neuropsychopharmacology (ACNP); December 5-9, 2009; Hollywood, FL.
17	Sliwa JK, Fu DJ, Bossie CA, et al. Body mass index and metabolic parameters in patients with schizophrenia during long-term treatment with paliperidone palmitate. BMC Psychiatry. 2014;14:52.
18	Pandina G, Lane R, Gopal S, et al. A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(1):218-226.
19	Hough D, Lindenmayer JP, Gopal S, et al. Safety and tolerability of deltoid and gluteal injections of paliperidone palmitate in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(6):1022-1031.
20	McEvoy JP, Byerly M, Hamer RM, et al. Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial. JAMA. 2014;311(19):1978-1987.
21	Takahashi N, Takahashi M, Saito T, et al. Randomized, placebo-controlled, double-blind study assessing the efficacy and safety of paliperidone palmitate in Asian patients with schizophrenia. Neuropsychiatr Dis Treat. 2013;9:1889-1898.
22	Fleischhacker WW, Gopal S, Lane R, et al. A randomized trial of paliperidone palmitate and risperidone long-acting injectable in schizophrenia. Int J Neuropsychopharmacol. 2012;15(1):107-118.
23	Sajatovic M, Doring M, Lopena OJ, et al. Earlier use of long-acting injectable paliperidone palmitate once-monthly versus oral antipsychotics in patients with schizophrenia: an integrated patient-level meta analysis of the PROSIPAL and PRIDE studies. Neuropsychiatr Dis Treat. 2024;20:2227-2235.
24	Zhang F, Si T, Chiou CF, et al. Efficacy, safety, and impact on hospitalizations of paliperidone palmitate in recent-onset schizophrenia. Neuropsychiatr Dis Treat. 2015;11:657-668.
25	Wakamatsu A, Takahashi N, Takahashi M, et al. A 57-week, open-label evaluation of paliperidone palmitate flexible doses in Japanese patients with schizophrenia. Poster presented at: 26th European College of Neuropsychopharmacology (ECNP) Congress; October 5-9, 2013; Barcelona, Spain.
26	Fu DJ, Turkoz I, Simonson RB, et al. Paliperidone palmitate long-acting injectable in acute exacerbation of schizoaffective disorder. Poster presented at: the 14th International Congress on Schizophrenia Research; April 21-25, 2013; Orlando, FL.
27	Huang M, Yu L, Pan F, et al. A randomized, 13-week study assessing the efficacy and metabolic effects of paliperidone palmitate injection and olanzapine in first-episode schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:122-130.