Antipsychotic-induced Weight Gain (AIWG)
Conditions
Keywords
Antipsychotic-induced weight gain (AIWG), Obesity, Weight Gain, Mental disorders, Schizophrenia, Risperidone, Paliperidone, Quetiapine, Olanzapine
Brief summary
This Phase 2, double-blind, placebo-controlled, randomized study is to assess the safety, efficacy, and pharmacokinetics (PK) of miricorilant (CORT118335) in obese patients with schizophrenia treated with antipsychotic medications.
Detailed description
This is a randomized, double-blind, placebo-controlled study that will assess the safety, efficacy, and PK of miricorilant in obese patients with schizophrenia who are currently taking olanzapine, risperidone, paliperidone, or quetiapine. Patients who meet the criteria for the Study CORT118335-877 will be randomized on Day 1 to receive 600 mg miricorilant, 900 mg miricorilant, or placebo for 26 weeks.
Interventions
DRUGMiricorlilant
Miricorilant 600 mg (4 X 150 mg) for once-daily for oral dosing
DRUGPlacebo
Placebo for once-daily oral dosing
Sponsors
Corcept Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of schizophrenia * Are currently taking olanzapine, risperidone, paliperidone, or quetiapine and have gained weight from treatment while on these medications * Must be on a stable dose of medication for 1 month prior to Screening * Have a BMI ≥30 kg/m\^2.
Exclusion criteria
* Have a history of a medical condition affecting body weight (eg, poorly controlled hyper- or hypothyroidism; eating disorder such as anorexia, bulimia, or binge eating; or polycystic ovary syndrome) * Have poorly controlled diabetes mellitus * Have poorly controlled hypertension * Have a history of symptomatic hypotension * Have a history of orthostatic hypotension * Have a history of a seizure disorder.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Body Weight | Baseline Day 1 and Week 26 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight for Both Dose Levels of Miricorilant Combined Versus Placebo | Baseline Day 1 and Week 26 | — |
| Percentage of Patients Achieving a ≥5% Weight Loss for Miricorilant Versus Placebo | Baseline Day 1 to Week 26 | Percentage of patients achieving a ≥5% weight loss for 600 mg miricorilant versus placebo and 900 mg miricorilant versus placebo |
| Change From Baseline in Waist-to-hip Ratio for Miricorilant Versus Placebo | Baseline Day 1 and Week 26 | — |
Other
| Measure | Time frame |
|---|---|
| Number of Patients With One or More Treatment-emergent Serious Adverse Events | Baseline Day 1 to Week 30 |
| Number of Patients With One or More Treatment-emergent Adverse Events Leading to Study Drug Discontinuation | Baseline Day 1 to Week 30 |
| Number of Patients With One or More Treatment-emergent Adverse Events | Baseline Day 1 to Week 30 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Miricorlilant 600 mg Patients who meet the entry criteria will be randomized to receive 600 mg miricorilant for 26 weeks.
Miricorlilant: Miricorilant 600 mg (4 X 150 mg) tablets for once-daily oral dosing | 50 |
| Miricorlilant 900 mg Patients who meet the entry criteria will be randomized to receive 900 mg miricorilant for 26 weeks.
Miricorlilant: Miricorilant 900 mg (6 X 150 mg) tablets for once-daily oral dosing | 48 |
| Placebo Patients who meet the entry criteria will be randomized to receive placebo for 26 weeks.
Placebo: Placebo for once-daily oral dosing | 52 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 4 |
| Overall Study | Lost to Follow-up | 3 | 4 | 3 |
| Overall Study | Moved | 0 | 1 | 0 |
| Overall Study | Non-compliant with study drug | 1 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 10 | 3 | 8 |
Baseline characteristics
| Characteristic | Miricorlilant 600 mg | Total | Placebo | Miricorlilant 900 mg |
|---|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 10.8 | 46.5 years STANDARD_DEVIATION 10.61 | 47.5 years STANDARD_DEVIATION 10.27 | 46.4 years STANDARD_DEVIATION 10.88 |
| Body weight | 115.41 kg STANDARD_DEVIATION 24.24 | 113.98 kg STANDARD_DEVIATION 23.69 | 118.11 kg STANDARD_DEVIATION 25.71 | 108.02 kg STANDARD_DEVIATION 19.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 21 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 128 Participants | 48 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants | 85 Participants | 28 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 57 Participants | 21 Participants | 17 Participants |
| Region of Enrollment United States | 50 participants | 150 participants | 52 participants | 48 participants |
| Sex: Female, Male Female | 17 Participants | 54 Participants | 18 Participants | 19 Participants |
| Sex: Female, Male Male | 33 Participants | 96 Participants | 34 Participants | 29 Participants |
| Waist-to-hip ratio | 0.991 Ratio STANDARD_DEVIATION 0.07 | 0.994 Ratio STANDARD_DEVIATION 0.07 | 0.992 Ratio STANDARD_DEVIATION 0.08 | 0.999 Ratio STANDARD_DEVIATION 0.06 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 48 | 0 / 52 |
| other Total, other adverse events | 8 / 50 | 3 / 48 | 4 / 52 |
| serious Total, serious adverse events | 1 / 50 | 2 / 48 | 2 / 52 |
Outcome results
Primary
Change From Baseline in Body Weight
Time frame: Baseline Day 1 and Week 26
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had body weight measurements at Baseline and on Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Miricorlilant 600 mg | Change From Baseline in Body Weight | -1.41 kg | Standard Error 0.644 |
| Miricorlilant 900 mg | Change From Baseline in Body Weight | -0.91 kg | Standard Error 0.631 |
| Placebo | Change From Baseline in Body Weight | -1.66 kg | Standard Error 0.644 |
p-value: 0.78795% CI: [-1.52, 2.01]Mixed Models Analysis
p-value: 0.401895% CI: [-1.01, 2.51]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight for Both Dose Levels of Miricorilant Combined Versus Placebo
Time frame: Baseline Day 1 and Week 26
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had body weight measurements at Baseline and on Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Miricorlilant 600 mg | Change From Baseline in Body Weight for Both Dose Levels of Miricorilant Combined Versus Placebo | -1.16 kg | Standard Error 0.454 |
| Miricorlilant 900 mg | Change From Baseline in Body Weight for Both Dose Levels of Miricorilant Combined Versus Placebo | -1.65 kg | Standard Error 0.642 |
p-value: 0.522895% CI: [-1.03, 2.02]Mixed Models Analysis
Secondary
Change From Baseline in Waist-to-hip Ratio for Miricorilant Versus Placebo
Time frame: Baseline Day 1 and Week 26
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had weight and hip measurements at Baseline and on Week 26.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Miricorlilant 600 mg | Change From Baseline in Waist-to-hip Ratio for Miricorilant Versus Placebo | 0.002 Ratio | Standard Error 0.0077 |
| Miricorlilant 900 mg | Change From Baseline in Waist-to-hip Ratio for Miricorilant Versus Placebo | 0.009 Ratio | Standard Error 0.0075 |
| Placebo | Change From Baseline in Waist-to-hip Ratio for Miricorilant Versus Placebo | 0.002 Ratio | Standard Error 0.0077 |
p-value: 0.98795% CI: [-0.021, 0.021]Mixed Models Analysis
p-value: 0.462495% CI: [-0.013, 0.029]Mixed Models Analysis
Secondary
Percentage of Patients Achieving a ≥5% Weight Loss for Miricorilant Versus Placebo
Percentage of patients achieving a ≥5% weight loss for 600 mg miricorilant versus placebo and 900 mg miricorilant versus placebo
Time frame: Baseline Day 1 to Week 26
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had Baseline and ≥1 body weight measurement on or after Week 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorlilant 600 mg | Percentage of Patients Achieving a ≥5% Weight Loss for Miricorilant Versus Placebo | 12 Participants |
| Miricorlilant 900 mg | Percentage of Patients Achieving a ≥5% Weight Loss for Miricorilant Versus Placebo | 7 Participants |
| Placebo | Percentage of Patients Achieving a ≥5% Weight Loss for Miricorilant Versus Placebo | 8 Participants |
p-value: 0.253795% CI: [0.661, 4.802]Regression, Logistic
p-value: 0.87495% CI: [0.308, 2.722]Regression, Logistic
Other Pre-specified
Number of Patients With One or More Treatment-emergent Adverse Events
Time frame: Baseline Day 1 to Week 30
Population: The Safety Population was patients who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorlilant 600 mg | Number of Patients With One or More Treatment-emergent Adverse Events | 26 Participants |
| Miricorlilant 900 mg | Number of Patients With One or More Treatment-emergent Adverse Events | 21 Participants |
| Placebo | Number of Patients With One or More Treatment-emergent Adverse Events | 21 Participants |
Other Pre-specified
Number of Patients With One or More Treatment-emergent Adverse Events Leading to Study Drug Discontinuation
Time frame: Baseline Day 1 to Week 30
Population: The Safety Population was patients who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorlilant 600 mg | Number of Patients With One or More Treatment-emergent Adverse Events Leading to Study Drug Discontinuation | 7 Participants |
| Miricorlilant 900 mg | Number of Patients With One or More Treatment-emergent Adverse Events Leading to Study Drug Discontinuation | 5 Participants |
| Placebo | Number of Patients With One or More Treatment-emergent Adverse Events Leading to Study Drug Discontinuation | 4 Participants |
Other Pre-specified
Number of Patients With One or More Treatment-emergent Serious Adverse Events
Time frame: Baseline Day 1 to Week 30
Population: The Safety Population was patients who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorlilant 600 mg | Number of Patients With One or More Treatment-emergent Serious Adverse Events | 1 Participants |
| Miricorlilant 900 mg | Number of Patients With One or More Treatment-emergent Serious Adverse Events | 2 Participants |
| Placebo | Number of Patients With One or More Treatment-emergent Serious Adverse Events | 2 Participants |