ALK3831-A307 Effect of ALKS3831 vs Olanzapine on body weight
Research type
Research Study
Full title
A Study to 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
IRAS ID
242931
Contact name
Ekwere George Umoh
Contact email
Sponsor organisation
Alkermes Inc
Eudract number
2017-000497-11
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 3 months, 25 days
Research summary
Summary of Research
This is a multicentre study which main purpose is to evaluate the effect of study medicine called ALKS 3831, compared to medicine called olanzapine, on body weight gain in young adults with schizophrenia, schizophreniform disorder or bipolar I disorder, who are early in their illness.
The study comprises of 3 phases:
- Screening period - up to 4 weeks
- Treatment period - 12 weeks
- Follow up period – 4 weeks
The study will last approximately 16 to 20 weeks. Patients will be required to attend 9 to 11 visits at the study centre. At study visit 1 eligible patients will be randomly assigned, at ratio 1:1, to receive ALKS 3831 or olanzapine. Neither the patient nor the study doctor will know which treatment patient is receiving.
During the study patient will have physical examination, an Electrocardiogram (ECG) and blood and urine tests. Patient will also have interviews and will be required to complete questionnaires.
Patients who complete 12 weeks of study treatment will be able to participate in a long-term extension study and receive the study medicine for another up to 2 years.
Patients who decide not to participate in the extension study will complete the safety follow-up period and return to standard of care treatment.
About 350 people globally will take part in this study.Summary of Results
Subject Disposition and Baseline Characteristics: Of the 428 subjects randomized, a total of 426 received at least 1 dose of study drug. Of the subjects who received at least 1 dose of study drug, a total of 326 (76.5%) completed the study. The most common reasons for early termination included withdrawal by subject (43, 10.1%), lost to follow-up (24, 5.6%), and adverse events (AE) (23, 5.4%). A total of 74 subjects entered the 4-week Safety Follow-up Period. A total of 251 (58.9%) subjects continued into the Long-term Safety Extension Study (ALK3831-A308).
A greater number of subjects were male (282, 66.2%), and most were White (283, 66.4%) or Black (120, 28.2%). The average BMI was 23.69 kg/m2, with 60.1% (N=256) of subjects having a normal BMI at baseline. The diagnosis at randomization was schizophrenia (268, 62.9%), schizophreniform disorder (66, 15.5%), or bipolar I disorder (92, 21.6%).
EFFICACY
∙ ALKS 3831 met the primary efficacy endpoint for percent change in body weight at Week 12, as the LS mean percent change from baseline was 4.91% for ALKS 3831 and 6.77% for OLZ (P=0.012).
∙ Secondary endpoints were evaluated with a hierarchical testing strategy as follows:
o The proportion of subjects with ≥10% weight gain at Week 12 was numerically smaller for ALKS 3831 (21.9%) than OLZ (30.4%), but the treatment difference was not statistically significant (P=0.075); therefore, P-values for the remaining secondary endpoints are not reported.
o The proportion of subjects with ≥7% weight gain at Week 12 was smaller for ALKS 3831 (33.1%) than OLZ (44.8%).
o Changes from baseline in waist circumference at Week 12 were numerically smaller for ALKS 3831 (2.99 cm) compared to OLZ (3.90 cm).
o The change from baseline in CGI-S at Week 12 for ALKS 3831 was -0.82, which demonstrated symptom improvement.
∙ Subgroup analyses of the primary and secondary endpoints were generally consistent with the primary analyses.
∙ Analyses for the other efficacy endpoints, absolute change in body weight, BMI, and body composition endpoints were generally supportive of the primary efficacy endpoint.
∙ Changes in fasting lipids and glycemic laboratory parameters tended to occur early in treatment and were generally small and similar for ALKS 3831 and OLZ at Week 12.
∙ No differences were observed for other efficacy endpoints: blood pressure, inflammatory markers, metabolic syndrome, IWQOL-Lite total scores and subscales.
∙ Analyses of change in CGI-S by visit and by diagnosis were consistent with findings for the secondary endpoint of change in CGI-S within the ALKS 3831 group and demonstrated similar patterns for ALKS 3831 and OLZ.
SAFETY
∙ In general, ALKS 3831 was well-tolerated, with a safety profile similar to OLZ, and consistent with previous studies of ALKS 3831. Similar proportions of subjects in both treatment groups experienced SAEs, AEs leading to discontinuation, and AEs to evaluate for EPS and suicidal ideation and behavior.
∙ Weight increased was the most common AE; other common AEs included Somnolence, Alanine aminotransferase increased, Headache, Sedation, Waist circumference increased, and Anxiety.
∙ SAEs of death (N=1) and suicidal ideation (N=3) were considered not related to study drug.
∙ Clinical laboratory evaluations, vital signs, ECGs, and physical exam findings did not have any unexpected clinically significant findings.
o Clinically significant findings for these metrics were generally as expected and may be related to the expected weight gain and metabolic effects with the study drugs.
OVERALL CONCLUSIONS
∙ Overall, in a population that included patients with schizophrenia, schizophreniform disorder or bipolar I disorder who were early in their illness, ALKS 3831 demonstrated less weight gain than OLZ, while maintaining a similar efficacy and safety profile.REC name
East Midlands - Derby Research Ethics Committee
REC reference
18/EM/0061
Date of REC Opinion
1 May 2018
REC opinion
Further Information Favourable Opinion