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INVEGA SUSTENNA®

(paliperidone palmitate)

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INVEGA SUSTENNA - Comparative Efficacy (PRIDE Study)

Last Updated: 08/19/2024

Overview1

The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study was a 15-month, US, prospective, randomized, open-label, event monitoring board-blinded, multicenter, comparative study of INVEGA SUSTENNA vs OAPs on time to first treatment failure in patients with schizophrenia recently released from incarceration

(N=444)

Inclusion Criteria1

  • Adult patients (age, 18-65 years)
  • Placed in custody ≥2 times in previous 2 years, with ≥1 event leading to incarceration
  • Custodial release within 90 days of screening

Exclusion Criteria1

  • Clozapine/injectable antipsychotic drug use (within 3 months of screening)
  • IV drug abuse (within 3 months of screening) or opioid dependence disorder

Study Design1

Efficacy Outcomes1

  • Median time to first treatment failure was significantly longer in the INVEGA SUSTENNA vs OAP group (416 vs 226 days; P=0.011)
  • Fewer patients reported treatment failure in INVEGA SUSTENNA vs OAP group (39.8% vs 53.7%)
  • Risk of first psychiatric hospitalization or arrest/incarceration was higher in OAP vs INVEGA SUSTENNA group (1.43×; 95% CI, 1.09-1.88)

Safety Outcomes
(INVEGA SUSTENNA vs OAP)1

TEAEs >10% in either arm

  • Injection site pain: 18.6% vs 0%
  • Insomnia: 16.8% vs 11.5%
  • Weight gain: 11.9% vs 6.0%
  • Akathisia: 11.1% vs 6.9%
  • Anxiety: 10.6% vs 7.3%

Other Safety Outcomes

  • Weight gain (≥7%): 32.4% vs 14.4%
  • Prolactin-related TEAEs: 23.5% vs 4.1%
  • TEAEs leading to drug discontinuation: 11.9% vs 7.8%

Results of Post Hoc Analyses

  • The median time to first treatment failure and to first psychiatric hospitalization or arrest/incarceration in the Black/African American patient subgroup was greater in the INVEGA SUSTENNA vs OAP group2
  • In the substance abuse and non-abuse cohorts, a higher risk of treatment failure was observed with OAP vs INVEGA SUSTENNA therapy3
  • The mean cumulative function of number of treatment failures and institutionalizations was significantly lower in the INVEGA SUSTENNA vs OAP group4
  • The risk of treatment failure was lower with INVEGA SUSTENNA vs A-OAP, C-OAP, and PAL+RIS5 5
  • Fewer treatment failures were reported in the PP group vs OAPs regardless of illness duration (0-3 years and >3 years).6,7

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. The conversion factor from mg eq. to mg is 1.56.

Note: A-OAP, atypical OAP; CI, confidence interval; C-OAP, conventional OAP; IM, intramuscular; ITT, intention-to-treat; IV, intravenous; OAP, oral antipsychotic; PAL+RIS, oral paliperidone and risperidone; PP, paliperidone palmitate 1-month or 3-month; TEAE, treatment-emergent adverse event; US, United States.

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. The conversion factor from mg eq. to mg is 1.56.

mg 39 78 117 156 234
mg eq. 25 50 75 100 150

PRIDE was a 15-month, prospective, randomized, open-label, event-monitoring board-blinded study in a community sample of patients from nontraditional locations (ie, homeless shelters, soup kitchens, jail-release or diversion programs) with schizophrenia, recently released from incarceration, receiving INVEGA SUSTENNA or OAPs daily.1

aClinician’s and patient’s joint review of available OAP for acceptability

Inclusion Criteria1 Exclusion Criteria1
  • Adult patients (age, 18-65 years) with schizophrenia per DSM-IV
  • Placed in custody ≥2 times in previous 2 years, with ≥1 event leading to incarceration
  • Release from most recent custody occurred within 90 days of screening
  • Use of either clozapine or an injectable antipsychotic within 3 months or 2 injection cycles of screening, respectively
  • Substance abuse was not exclusionary; however, patients abusing IV drugs within 3 months of screening or with an opiate dependence disorder were excluded
Inclusion Criteria1
  • Adult patients (age, 18-65 years) with schizophrenia per DSM-IV
  • Placed in custody ≥2 times in previous 2 years, with ≥1 event leading to incarceration
  • Release from most recent custody occurred within 90 days of screening
Exclusion Criteria1
  • Use of either clozapine or an injectable antipsychotic within 3 months or 2 injection cycles of screening, respectively
  • Substance abuse was not exclusionary; however, patients abusing IV drugs within 3 months of screening or with an opiate dependence disorder were excluded

Primary Efficacy Endpoint1

  • Time to first treatment failure defined as:
    • arrest or incarceration
    • psychiatric hospitalization
    • suicide
    • treatment discontinuation due to inadequate efficacy, safety, or tolerability
    • treatment supplementation due to inadequate efficacy, or
    • increase in level of psychiatric services to prevent imminent psychiatric hospitalization

Secondary Efficacy Endpoints1

  • Time to first psychiatric hospitalization or arrest/incarceration
  • Change in PSP scores
  • Change in CGI-S score
  • Demographics and baseline characteristics were similar between treatment groups.1

Baseline Characteristics1

Baseline Characteristics INVEGA SUSTENNA
(n=226)
OAP
(n=218)
Age, years, mean (SD) 37.7 (10.6) 38.6 (10.4)
Male, n (%) 193 (85.4) 190 (87.2)
Race, n (%)
White 73 (32.3) 74 (34.1)a
Black/African American 145 (64.2) 130 (59.9)a
Others 8 (3.5) 13 (6.0)a
Time since release from last incarceration, mean, days 38.9 45.7a
Concurrent substance abuse, n (%) 130 (57.5) 134 (61.5)
Number of psychiatric hospitalizations, mean 7.3b 5.7c
PSP total score, mean (SD) 54.8 (12.8) 55.0 (12.7)d
CGI-S score, mean (SD) 3.8 (0.8) 3.9 (0.7)a
an=217; bn=176; cn=170; dn=215.
  • The mean exposure to INVEGA SUSTENNA was 266.2 days and to OAP was 271.5 days.1

Mean Drug Doses1

INVEGA SUSTENNA HAL PER ARI OLA QUE PAL RIS
Mean dose, mg 181.3a
(n=226)
7.7b
(n=11)
14.4b
(n=18)
16.6b
(n=25)
13.2b
(n=31)
335.9b
(n=24)
6.4b
(n=43)
3.4b
(n=30)
aDose per injection records; bDose per refill records.
  • The median time to first treatment failure was significantly longer for INVEGA SUSTENNA vs OAP (416 vs 226 days; P=0.011).1
  • Treatment failure was reported in 68.7% of patients overall, and in 39.8% vs 53.7% of patients in the INVEGA SUSTENNA vs OAP group, respectively.1
  • Risk of treatment failure was 1.43 times higher in the OAP vs INVEGA SUSTENNA group (95% CI, 1.09-1.88).1
  • A significantly longer time to first psychiatric hospitalization or arrest/incarceration was observed with INVEGA SUSTENNA vs OAP (P=0.019).1
    • The risk of first psychiatric hospitalization or arrest/incarceration was 1.43 times higher in the OAP vs INVEGA SUSTENNA group (95% CI, 1.06-1.93).
  • No significant between-group differences were observed in mean change in PSP total scores (least squares mean [SE] difference=0.39 [0.98]) and CGI-S scores (least squares mean [SE] difference= -0.06 [0.05]).1

Treatment-Emergent Adverse Events1

  • Most common AEs reported were injection site pain, insomnia, weight gain, akathisia, and anxiety in the INVEGA SUSTENNA group; and insomnia, headache, dry mouth, anxiety, and sedation in the OAP group.
  • Serious TEAEs were reported in 17.3% of patients receiving INVEGA SUSTENNA and 21.6% of patients receiving OAP.
  • TEAEs leading to drug discontinuation occurred in 11.9% of patients receiving INVEGA SUSTENNA and 7.8% of patients receiving OAP.
  • A treatment-emergent prolactin-related AE was reported in 23.5% (n=53) of patients receiving INVEGA SUSTENNA and 4.1% (n=9) of patients receiving OAP.
  • Rates of EPS-related TEAEs for the INVEGA SUSTENNA and OAP groups, respectively, were as follows: akathisia (11.1% vs 6.9%), dyskinesia (2.7% vs 1.4%), dystonia (2.2% vs 2.8%), and parkinsonism (1.8%, each).
  • Weight gain increase ≥7% was observed in 32.4% of INVEGA SUSTENNA and 14.4% of OAP patients.

Bell Lynum et al (2021)2

Objective: To evaluate the efficacy of INVEGA SUSTENNA vs OAP in delaying time to first relapse in Black/African American patients (N=275)

Parameter INVEGA SUSTENNA vs OAP
  • Median time to first treatment
    failure
NR (>450 days) vs 270 days
HR, 1.39 (95% CI, 0.97-1.99); P=0.075
  • Median time to first psychiatric
    hospitalization or arrest/incarceration
NR (>450 days) vs 304 days
HR, 1.49 (95% CI, 1.01-2.19); P=0.043
  • TEAEs
86.9% vs 83.1%
  • TEAE-related treatment discontinuation
11.0% vs 5.4%

Most frequently reported TEAEs (≥10% in either group): injection site pain, insomnia, akathisia, weight gain, headache, and dry mouth.

The median time to treatment failure and to first psychiatric hospitalization or arrest/incarceration were greater in the INVEGA SUSTENNA vs OAP group.

Starr et al (2018)3

Objective: To evaluate the impact of substance abuse on treatment failure with INVEGA SUSTENNA vs OAP

Greater treatment effects were seen with INVEGA SUSTENNA compared with OAP in both the substance abuse and nonabuse cohorts. The effect of INVEGA SUSTENNA vs OAP was attenuated in the substance abuse cohort.

Most frequently reported TEAEs (≥20% in either group and cohort): weight gain, EPS-related TEAEs, prolactin-related TEAEs, injection site pain, and insomnia.

Median Time to Key Events, Days Substance Abuse Cohort
Treatment failure 291 vs 186
Psychiatric hospitalization or arrest/incarceration 371 vs 317
Median Time to Key Events, Days Nonabuse Cohort
Treatment failure >450 vs 284
Psychiatric hospitalization or arrest/incarceration >450 vs 371
Median Time to Key Events, Days Substance Abuse Cohort Nonabuse Cohort
Treatment failure 291 vs 186 >450 vs 284
Psychiatric hospitalization or arrest/ incarceration 371 vs 317 >450 vs 371

Alphs et al (2016)4

Objective: To compare the mean cumulative function of treatment failure and safety in INVEGA SUSTENNA vs OAP group

Parameter INVEGA SUSTENNA vs OAP
  • Mean cumulative function of treatment
    failure
1.02 vs 1.50 (P=0.007)
  • Mean cumulative function of
    institutionalizationa
0.82 vs 1.27 (P=0.005)
  • TEAEs
86.3% vs 81.7%
  • TEAE-related treatment discontinuation
12.4% vs 8.7%

The mean cumulative function of treatment failure and institutionalization was significantly lower in the INVEGA SUSTENNA vs OAP group.

aArrests, incarcerations, or psychiatric hospitalizations.

Kim et al (2016)5

Objective: To evaluate the efficacy and safety of INVEGA SUSTENNA vs 3 OAP subgroups

The risk of treatment failure was lower with
INVEGA SUSTENNA vs A-OAP, C-OAP, and PAL+RIS.

Most common TEAEs in ≥10% of subjects in either group, were injection site pain, insomnia, weight gain, akathisia, and anxiety (similar to PRIDE study).

TEAE Category INVEGA SUSTENNA OAP Groups
≥7% weight increase 32.4% 11.4% (C-OAP)
14.9% (A-OAP)
16.0% (PAL+RIS)
EPS-related 23.9% 45.7% (C-OAP)
13.7% (A-OAP)
10.6% (PAL+RIS)
Prolactin-related 23.5% 5.7% (C-OAP)
3.8% (A-OAP)
3.5% (PAL+RIS)

aHAL and PER; bARI, OLA, QUE, PAL, and RIS.

Lopena et al (2023)6

Objective: A post hoc analysis to assess the efficacy and safety of PP (INVEGA SUSTENNA or INVEGA TRINZA) vs OAP treatment in adult patients diagnosed with schizophrenia and with varying duration of illness (0-3 and >3 years) using data from the PRIDE, PROSIPAL, and DREaM studies.

Parameter: Efficacy and safety outcomes including relapse assessments, the PSP scale scores, the MSQ total scores, and TEAEs.

Baseline Characteristics: A total of 1,247 patients were included in the ITT analysis set (0-3 years: PP, n=294; OAP, n=312; >3 years: PP, n=325; OAP, n=316). Most patients were male (69.5%), and the mean age was 33.9 years.

Efficacy:

  • Fewer treatment failures were observed with PP vs OAP in both the 0-3 years (17.7% vs 25.3%) and >3 years (32.3% vs 42.4%) groups.
  • TtFTF was significantly longer with PP vs OAP treatment in both the duration of illness groups (0-3 years: HR, 0.67; 95% CI: 0.47-0.95; P=0.026 and >3 years: HR, 0.69; 95% CI: 0.53-0.89; P=0.004).
  • The mean PSP scale scores increased from 55.4 to 66.1 in the 0-3 years group and 56.5 to 65.4 in the >3 years group from baseline to endpoint (15 months).
  • In the 0-3 years group, the mean (SD) MSQ score increased from 5.0 (1.10) to 5.2 (1.25) in the PP group and 4.9 (1.02) to 5.1 (1.21) in the OAP group from the baseline to endpoint (12 months).
  • Similarly, in the >3 years group, the mean (SD) MSQ scores increased from 4.6 (1.36) to 5.1 (1.55) in the PP group and 4.7 (1.28) to 5.2 (1.43) in the OAP group.

Safety:

  • A total of 957 (76.7%) patients experienced a TEAE:
    • 0-3 years: PP, n=235 (79.9%); OAP, n=226 (72.4%)
    • >3 years: PP, n=254 (78.2%); OAP, n=242 (76.6%)total of 957 (76.7%) patients experienced a TEAE
  • The most common TEAEs were weight increase, insomnia, headache, and injection site pain.
  • In the 0-3 years group, SAEs occurred in 31 (10.5%) and 47 (15.1%) patients treated with PP and OAP, respectively.
  • In the >3 years group, SAEs occurred in 57 (17.5%) and 65 (20.6%) patients treated with PP and OAP, respectively.

In the pooled data from the PRIDE, PROSIPAL, and DREaM studies, fewer treatment failures were reported in the PP group vs OAPs regardless of duration of illness (0-3 years vs >3 years).

Sajatovic et al (2024)7

Objective: 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.

Parameter: Time to treatment failure or relapse as defined in each study and TEAEs.

Baseline Characteristics: 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). Most patients were male (68.7%), and the mean age was 34.7 years.

Efficacy:

  • Fewer relapses were reported in the patients who received INVEGA SUSTENNA vs OAP (25.2% vs 32.9%).
  • The overall risk of relapse was reduced by 31% in the patients who received INVEGA SUSTENNA vs OAP (HR, 0.69; 95% CI, 0.56-0.86; P<0.001).
  • Reductions in the risk of relapse by duration of illness for patients receiving INVEGA SUSTENNA vs OAPs were:
    • 0-3 years: 33% reduction (HR, 0.67; 95% CI, 0.44-1.00; P=0.050)
    • >3-5 years: 43% reduction (HR, 0.57; 95% CI, 0.35-0.93; P=0.025)
    • >5 years: 26% reduction (HR, 0.74; 95% CI, 0.55-1.00; P=0.049)

Safety:

  • The most common TEAEs (≥10%) were injection site pain, nasopharyngitis, weight increase, akathisia, headache, anxiety, insomnia, and schizophrenia.
  • A total of 875 (75.6%) patients experienced a TEAE:
    • 0-3 years: INVEGA SUSTENNA, n=197 (77.9%); OAP, n=182 (69.2%)
    • >3-5 years: INVEGA SUSTENNA, n=99 (71.7%); OAP, n=93 (69.4%)
    • >5 years: INVEGA SUSTENNA, n=155 (82.9%); OAP, n=149 (81.9%)

In the pooled data from the PRIDE and PROSIPAL studies, fewer relapses were reported in the patients treated with INVEGA SUSTENNA vs OAP regardless of duration of illness (0-3 years vs >3-5 years vs >5 years).

AE Adverse event OAP Oral antipsychotic
A-OAP Atypical OAP OLA Olanzapine
ARI Aripiprazole PAL Paliperidone
CGI-S Clinical Global Impressions-Severity of Illness Scale PAL+RIS Oral paliperidone and risperidone
CI Confidence interval PER Perphenazine
C-OAP Conventional OAP PP Paliperidone palmitate 1-month or 3-month
DSM-IV Diagnostic and Statistical Manual of Mental Disorders 4th edition PRIDE Paliperidone Palmitate Research In Demonstrating Effectiveness
EPS Extrapyramidal symptom PSP Personal and Social Performance Scale
HAL Haloperidol QUE Quetiapine
HR Hazard ratio RIS Risperidone
IM Intramuscular SD Standard deviation
ITT Intention-to-treat SE Standard error
IV Intravenous TEAE Treatment-emergent AE
MSQ Medication Satisfaction Questionnaire US United Sates
NR Not reached TtFTF Time to first treatment failure
  1. 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.
  2. Bell Lynum KS, Henderson DC, Wright HJ, et al. Treatment effect with paliperidone palmitate compared with oral antipsychotics in Black/African American patients with schizophrenia and a history of criminal justice system involvement: a post hoc analysis of the PRIDE study. J Clin Psychiatry. 2021;82(2):20m13356.
  3. Lynn Starr H, Bermak J, Mao L, et al. Comparison of long-acting and oral antipsychotic treatment effects in patients with schizophrenia, comorbid substance abuse, and a history of recent incarceration: an exploratory analysis of the PRIDE study. Schizophr Res. 2018;194:39-46.
  4. Alphs L, Mao L, Lynn Starr H, et al. A pragmatic analysis comparing once-monthly paliperidone palmitate versus daily oral antipsychotic treatment in patients with schizophrenia. Schizophr Res. 2016;170(2-3):259-264.
  5. Kim E, Correll CU, Mao L, et al. Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia. CNS Spectr. 2016;21(6):466-477.
  6. Lopena OJ, Alphs LD, Sajatovic M, et al. Earlier use of long-acting injectable paliperidone palmitate versus oral antipsychotics in patients with schizophrenia: an integrated patient-level post-hoc analysis. J Clin Psychiatry. 2023;84:(6):23m14788.
  7. Sajatovic M, Lopena O, Johnston K, et al. Earlier use of long-acting injectable paliperidone palmitate versus oral antipsychotics in patients with schizophrenia: an integrated patient-level post hoc analysis of the PRIDE and PROSIPAL studies. Poster presented at: Psych Congress Elevate; May 30-June 2, 2024; Las Vegas, NV.