Antipsychotic-induced Weight Gain (AIWG)
Conditions
Keywords
Antipsychotic-induced weight gain (AIWG), Obesity, Weight Gain, Mental disorders, Schizophrenia, Risperidone, Quetiapine, Olanzapine, Bipolar Disorder
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 adults with schizophrenia or bipolar disorder 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 or bipolar disorder who are currently taking oral or injectable atypical antipsychotic medication. Patients who meet the criteria for the Study CORT118335-876 will be randomized on Day 1 to receive 600 mg miricorilant or placebo for 12 weeks.
Interventions
DRUGMiricorilant
Miricorilant 600 mg (6 X 100 mg tablets) for once-daily oral dosing
DRUGPlacebo
Placebo tablets 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 or bipolar disorder * Are currently taking oral or injectable atypical antipsychotic medication (except clozapine) and must have documented weight gain while on these medications * Must be on a stable dose of medication for 1 month prior to Screening * Are able to successfully complete placebo tablet swallow test * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Body Weight at Week 12 for 600 mg Miricorilant Versus Placebo | Baseline Day 1 and Week 12 |
| Number of Patients With One or More Treatment-emergent Adverse Events | Up to Follow-up Visit (Week 16) |
| Number of Patients With One or More Treatment-emergent Serious Adverse Events | Up to Follow-up Visit (up to Week 16) |
| Number of Patients With One or More Treatment-emergent Adverse Events Leading to Early Study Discontinuation | Up to Follow-up Visit (up to Week 16) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HOMA-IR at Week 12 | Baseline Day 1 and Week 12 | HOMA-IR = \[fasting plasma glucose (mg/dL) X fasting insulin (µU/mL)\]/405. HOMA-IR is a method to evaluate insulin sensitivity. The HOMA-IR score should be ≤1.0 to be considered normal. A score \>1.9 indicates early insulin resistance and a score \>2.9 indicates significant insulin resistance. |
| Change From Baseline in Waist-to-hip Ratio at Week 12 | Baseline Day 1 and Week 12 | Waist-to-hip ratio compares the circumference of the waist to the circumference of the hips. The ratio is calculated by dividing the waist measurement by the hip measurement, using the same units of measurement for both. A waist-to-hip ratio \<0.95 in men and \<0.80 in women is considered healthy. |
| Percentage of Patients Achieving More Than or Equal to 5% Weight Loss | Baseline Day 1 to Week 12 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Miricorilant 600 mg Patients who meet the entry criteria will be randomized to receive 600 mg miricorilant for 12 weeks.
Miricorilant: Miricorilant 600 mg (6 X 100 mg tablets) for once-daily oral dosing | 35 |
| Placebo Patients who meet the entry criteria will be randomized to receive placebo for 12 weeks.
Placebo: Placebo tablets for once daily oral dosing | 36 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Gaining weight without prohibited medication vyvanse | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 5 |
| Overall Study | Non-compliant with investigational product | 1 | 0 |
| Overall Study | Not reporting for scheduled visits | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Miricorilant 600 mg |
|---|---|---|---|
| Age, Continuous | 47.5 Years STANDARD_DEVIATION 11.78 | 45.7 Years STANDARD_DEVIATION 11.24 | 43.9 Years STANDARD_DEVIATION 10.5 |
| Body weight | 107.69 kg STANDARD_DEVIATION 25.41 | 109.02 kg STANDARD_DEVIATION 22.79 | 110.39 kg STANDARD_DEVIATION 20.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 16 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 55 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Homeostatic model assessment for insulin resistance (HOMA-IR) | 8.463 HOMA-IR score STANDARD_DEVIATION 17.27 | 8.577 HOMA-IR score STANDARD_DEVIATION 13.24 | 8.687 HOMA-IR score STANDARD_DEVIATION 5.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 29 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 41 Participants | 21 Participants |
| Region of Enrollment United States | 36 participants | 71 participants | 35 participants |
| Sex: Female, Male Female | 20 Participants | 39 Participants | 19 Participants |
| Sex: Female, Male Male | 16 Participants | 32 Participants | 16 Participants |
| Waist-to-hip ratio | 0.967 Ratio STANDARD_DEVIATION 0.1 | 0.999 Ratio STANDARD_DEVIATION 0.18 | 1.032 Ratio STANDARD_DEVIATION 0.24 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 36 |
| other Total, other adverse events | 12 / 35 | 5 / 36 |
| serious Total, serious adverse events | 1 / 35 | 1 / 36 |
Outcome results
Primary
Change From Baseline in Body Weight at Week 12 for 600 mg Miricorilant Versus Placebo
Time frame: Baseline Day 1 and Week 12
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had body weight assessed at Baseline and on Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Miricorilant 600 mg | Change From Baseline in Body Weight at Week 12 for 600 mg Miricorilant Versus Placebo | -0.98 kg | Standard Error 0.414 |
| Placebo | Change From Baseline in Body Weight at Week 12 for 600 mg Miricorilant Versus Placebo | -1.08 kg | Standard Error 0.415 |
p-value: 0.851195% CI: [-1.03, 1.24]Mixed Models Analysis
Primary
Number of Patients With One or More Treatment-emergent Adverse Events
Time frame: Up to Follow-up Visit (Week 16)
Population: The Safety Population included patients who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorilant 600 mg | Number of Patients With One or More Treatment-emergent Adverse Events | 16 Participants |
| Placebo | Number of Patients With One or More Treatment-emergent Adverse Events | 18 Participants |
Primary
Number of Patients With One or More Treatment-emergent Adverse Events Leading to Early Study Discontinuation
Time frame: Up to Follow-up Visit (up to Week 16)
Population: The Safety Population included patients who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorilant 600 mg | Number of Patients With One or More Treatment-emergent Adverse Events Leading to Early Study Discontinuation | 3 Participants |
| Placebo | Number of Patients With One or More Treatment-emergent Adverse Events Leading to Early Study Discontinuation | 1 Participants |
Primary
Number of Patients With One or More Treatment-emergent Serious Adverse Events
Time frame: Up to Follow-up Visit (up to Week 16)
Population: The Safety Population included patients who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorilant 600 mg | Number of Patients With One or More Treatment-emergent Serious Adverse Events | 1 Participants |
| Placebo | Number of Patients With One or More Treatment-emergent Serious Adverse Events | 1 Participants |
Secondary
Change From Baseline in HOMA-IR at Week 12
HOMA-IR = \[fasting plasma glucose (mg/dL) X fasting insulin (µU/mL)\]/405. HOMA-IR is a method to evaluate insulin sensitivity. The HOMA-IR score should be ≤1.0 to be considered normal. A score \>1.9 indicates early insulin resistance and a score \>2.9 indicates significant insulin resistance.
Time frame: Baseline Day 1 and Week 12
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had HOMA-IR assessed at Baseline and on Week 12.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Miricorilant 600 mg | Change From Baseline in HOMA-IR at Week 12 | 1.080 HOMA-IR score |
| Placebo | Change From Baseline in HOMA-IR at Week 12 | 0.890 HOMA-IR score |
p-value: 0.928595% CI: [-2.86, 2.78]Wilcoxon rank-sum test
Secondary
Change From Baseline in Waist-to-hip Ratio at Week 12
Waist-to-hip ratio compares the circumference of the waist to the circumference of the hips. The ratio is calculated by dividing the waist measurement by the hip measurement, using the same units of measurement for both. A waist-to-hip ratio \<0.95 in men and \<0.80 in women is considered healthy.
Time frame: Baseline Day 1 and Week 12
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had hip and waist measurements at Baseline and on Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Miricorilant 600 mg | Change From Baseline in Waist-to-hip Ratio at Week 12 | 0.008 Ratio | Standard Error 0.0092 |
| Placebo | Change From Baseline in Waist-to-hip Ratio at Week 12 | 0.001 Ratio | Standard Error 0.0091 |
p-value: 0.566995% CI: [-0.018, 0.033]Mixed Models Analysis
Secondary
Percentage of Patients Achieving More Than or Equal to 5% Weight Loss
Time frame: Baseline Day 1 to Week 12
Population: The Efficacy Evaluable Population was patients who received ≥4 weeks of study drug and had baseline and ≥1 body weight measurement taken on or after Week 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Miricorilant 600 mg | Percentage of Patients Achieving More Than or Equal to 5% Weight Loss | 2 Participants |
| Placebo | Percentage of Patients Achieving More Than or Equal to 5% Weight Loss | 3 Participants |
p-value: 0.816995% CI: [0.15, 4.474]Regression, Logistic