Bipolar I Disorder, Schizophrenia, Schizophreniform Disorders
Conditions
Keywords
Alkermes, ALKS 3831, Olanzapine, Samidorphan, Schizophrenia, Schizophreniform, Bipolar I
Brief summary
This study will evaluate the effect of ALKS 3831 compared to olanzapine on body weight in young adults with schizophrenia, schizophreniform, or bipolar I disorder who are early in their illness
Detailed description
In the US adolescent subjects starting at age 16 will be enrolled. In the EU, subjects age 18 and older will be enrolled.
Interventions
DRUGALKS 3831
Olanzapine + samidorphan, daily oral dosing
DRUGOlanzapine
Daily oral dosing
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Has less than 24 weeks previous treatment with antipsychotics (cumulative; lifetime) * Subject treated with aripiprazole can receive an additional 1 year of treatment at ≤5 mg/day, and this treatment will not be considered as part of the 24 weeks of previous treatment with antipsychotics * Has less than 4 years elapse since the initial onset of active-phase of symptoms * Has a body mass index (BMI) of \<30 kg/m\^2 * Agrees to use an acceptable method of contraception for the duration of the study and for 30 days after the last dose of study drug * Subject meets the criteria for a primary diagnosis of schizophrenia, schizophreniform disorder, or bipolar I disorder * For bipolar I disorder, must have been experiencing an episode of acute mania within ≤14 days prior to Visit 1 * Suitable for outpatient treatment * Additional criteria may apply
Exclusion criteria
* Poses a current suicide risk * Has a history of poor or inadequate response to treatment with olanzapine * Has previously been treated with long-acting injectable antipsychotic medication within the 2 months prior to screening, or has \> 6 months cumulative life use, or has received treatment with electroconvulsive therapy in their lifetime * Has initiated treatment with mood stabilizers (eg lithium, valproate, etc) \>2 months prior to Visit 1 * Has a positive drug screen for opioids, phencyclidine (PCP), amphetamine/methamphetamine, or cocaine * Has taken opioid agonists (eg, codeine, oxycodone, tramadol, morphine) within the 14 days prior to Visit 1, or has taken opioid antagonists, including naltrexone and naloxone, within 60 days prior to Visit 1 * Taking any weight loss agents or hypoglycemic agents * Has a clinically significant or unstable medical illness, condition, or disorder that would be anticipated to potentially compromise subject safety or adversely affect the evaluation of efficacy * Has joined a weight management program or had significant changes in diet or exercise regimen within the past 6 weeks * Has started a smoking cessation program within the past 6 months * Has a history of diabetes * Currently pregnant or breastfeeding or is planning to become pregnant during the study or within 30 days of the last study drug administration * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Week 12 | Baseline and 12 weeks | The efficacy analyses were performed using the Final Analysis Set which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With ≥10% Weight Gain at Week 12 | Baseline and 12 weeks | Percentage of weight gain is analyzed based on the subject's assessment status (≥10% vs \<10%) at Week 12 using a logistic regression model including treatment group, diagnosis (schizophrenia/schizophreniform disorder vs bipolar I disorder), region (US vs non-US), and baseline BMI (\<25 vs ≥25) as factors and baseline weight as covariate. |
| Percentage of Subjects With ≥7% Weight Gain at Week 12 | Baseline and 12 weeks | — |
| Number of Participants Experiencing of Adverse Events (AEs) | Up to 16 weeks | — |
| Change From Baseline in Waist Circumference at Week 12 | Baseline and Week 12 | — |
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score Within the ALKS 3831 Group at Week 12 | Baseline and Week 12 | Clinical Global Impression-Severity (CGI-S) Score is a 3-item, clinician-rated scale used to assess global illness severity, overall improvement from the start of treatment, and therapeutic response. It is a 7-point scale that requires the clinician to assess how mentally ill the patient is at a specific point in time. Based on the scale, patients are categorized as follows: 1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; and 7: among the most extremely ill patients. |
Countries
Austria, Germany, Ireland, Israel, Italy, Poland, Russia, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ALKS 3831 Coated bilayer tablet
ALKS 3831: Olanzapine + samidorphan, daily oral dosing | 211 |
| Olanzapine Coated bilayer tablet
Olanzapine: Daily oral dosing | 215 |
| Total | 426 |
Baseline characteristics
| Characteristic | ALKS 3831 | Olanzapine | Total |
|---|---|---|---|
| Age, Continuous | 26.0 years STANDARD_DEVIATION 6.12 | 25.7 years STANDARD_DEVIATION 5.92 | 25.8 years STANDARD_DEVIATION 24.5 |
| Clinical Global Impression-Severity (CGI-S) Score | 3.87 units on a scale STANDARD_DEVIATION 0.809 | — | 3.87 units on a scale STANDARD_DEVIATION 0.809 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 14 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 199 Participants | 201 Participants | 400 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 10 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 62 Participants | 58 Participants | 120 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 139 Participants | 144 Participants | 283 Participants |
| Region of Enrollment Austria | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Germany | 1 participants | 2 participants | 3 participants |
| Region of Enrollment Ireland | 1 participants | 3 participants | 4 participants |
| Region of Enrollment Israel | 20 participants | 12 participants | 32 participants |
| Region of Enrollment Italy | 9 participants | 4 participants | 13 participants |
| Region of Enrollment Poland | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Russia | 40 participants | 42 participants | 82 participants |
| Region of Enrollment South Korea | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Ukraine | 35 participants | 42 participants | 77 participants |
| Region of Enrollment United Kingdom | 2 participants | 1 participants | 3 participants |
| Region of Enrollment United States | 102 participants | 104 participants | 206 participants |
| Sex: Female, Male Female | 69 Participants | 75 Participants | 144 Participants |
| Sex: Female, Male Male | 142 Participants | 140 Participants | 282 Participants |
| Weight | 71.57 Kilogram (kg) STANDARD_DEVIATION 13.278 | 70.09 Kilogram (kg) STANDARD_DEVIATION 12.366 | 70.83 Kilogram (kg) STANDARD_DEVIATION 12.832 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 211 | 0 / 215 |
| other Total, other adverse events | 134 / 211 | 136 / 215 |
| serious Total, serious adverse events | 8 / 211 | 8 / 215 |
Outcome results
Primary
Percent Change From Baseline in Body Weight at Week 12
The efficacy analyses were performed using the Final Analysis Set which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug
Time frame: Baseline and 12 weeks
Population: The efficacy analyses were performed using the Final Analysis Set (FAS) which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ALKS 3831 | Percent Change From Baseline in Body Weight at Week 12 | 4.91 Percentage of change in body weight | Standard Error 0.597 |
| Olanzapine | Percent Change From Baseline in Body Weight at Week 12 | 6.77 Percentage of change in body weight | Standard Error 0.596 |
p-value: 0.01295% CI: [-3.33, -0.41]ANCOVA
Secondary
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score Within the ALKS 3831 Group at Week 12
Clinical Global Impression-Severity (CGI-S) Score is a 3-item, clinician-rated scale used to assess global illness severity, overall improvement from the start of treatment, and therapeutic response. It is a 7-point scale that requires the clinician to assess how mentally ill the patient is at a specific point in time. Based on the scale, patients are categorized as follows: 1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; and 7: among the most extremely ill patients.
Time frame: Baseline and Week 12
Population: The efficacy analyses were performed using the Final Analysis Set which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ALKS 3831 | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score Within the ALKS 3831 Group at Week 12 | -.82 units on a scale | Standard Error 0.06 |
Secondary
Change From Baseline in Waist Circumference at Week 12
Time frame: Baseline and Week 12
Population: The efficacy analyses were performed using the Final Analysis Set which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ALKS 3831 | Change From Baseline in Waist Circumference at Week 12 | 2.99 Centimeters | Standard Error 0.464 |
| Olanzapine | Change From Baseline in Waist Circumference at Week 12 | 3.90 Centimeters | Standard Error 0.477 |
Secondary
Number of Participants Experiencing of Adverse Events (AEs)
Time frame: Up to 16 weeks
Population: The safety population included all subjects who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALKS 3831 | Number of Participants Experiencing of Adverse Events (AEs) | 134 Participants |
| Olanzapine | Number of Participants Experiencing of Adverse Events (AEs) | 136 Participants |
Secondary
Percentage of Subjects With ≥10% Weight Gain at Week 12
Percentage of weight gain is analyzed based on the subject's assessment status (≥10% vs \<10%) at Week 12 using a logistic regression model including treatment group, diagnosis (schizophrenia/schizophreniform disorder vs bipolar I disorder), region (US vs non-US), and baseline BMI (\<25 vs ≥25) as factors and baseline weight as covariate.
Time frame: Baseline and 12 weeks
Population: The efficacy analyses were performed using the Final Analysis Set which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALKS 3831 | Percentage of Subjects With ≥10% Weight Gain at Week 12 | 21.9 Percentage of participants |
| Olanzapine | Percentage of Subjects With ≥10% Weight Gain at Week 12 | 30.4 Percentage of participants |
Secondary
Percentage of Subjects With ≥7% Weight Gain at Week 12
Time frame: Baseline and 12 weeks
Population: The efficacy analyses were performed using the Final Analysis Set which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALKS 3831 | Percentage of Subjects With ≥7% Weight Gain at Week 12 | 33.1 Percentage of participants |
| Olanzapine | Percentage of Subjects With ≥7% Weight Gain at Week 12 | 44.8 Percentage of participants |