ALK3831-A308 Long term safety extension study of ALKS3831
Research type
Research Study
Full title
A Phase 3 Study to Assess the Long Term Safety, Tolerability, and Durability of Treatment Effect of ALKS 3831 in Subjects with Schizophrenia, Schizophreniform Disorder, or Bipolar I Disorder
IRAS ID
242930
Contact name
Ekwere George Umoh
Contact email
Sponsor organisation
Alkermes Inc.
Eudract number
2017-000918-36
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 6 months, 0 days
Research summary
This is a multicentre, follow-up study of the ALK3831-A307 trial. The main purpose of the study is to evaluate the long term safety, tolerability and durability of treatment effect of the study medicine called ALKS 3831, in patients with schizophrenia, schizophreniform disorder or bipolar I disorder.
Treatment with ALKS 3831 has the potential to reduce the risk of weight gain which is a known side-effect of treatment with medicine called olanzapine, while having similar antipsychotic effect.
The study comprises of 2 phases:
- Treatment period – 24 months
- Follow up period – 4 weeks
In UK only patients who completed the main ALK3831-A307 study will be eligible to participate in this follow-up study.
Patients who agree to roll over into extension study will receive the study drug for another up to 2 years. 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.
After the completion of the follow up period patients will return to their normal standard of care treatment.
Approximately 500 patients globally will take part in the study.Summary of Results
Why was this study done?
Researchers are looking for better ways to treat mental health conditions like schizophrenia, schizophreniform disorder, and bipolar I disorder. These conditions have harmful effects to a patient’s way of living, like difficulties in taking care oneself or performing day-to-day tasks.
• Schizophrenia is a lifelong condition that affects how a person thinks, feels, and behaves. Schizophreniform disorder is similar to schizophrenia but lasts for a shorter period (less than 6 months).
• Bipolar disorder is a lifelong condition that causes abnormal changes in a person’s mood, energy, activity levels, and concentration.
The main questions that researchers wanted to answer in this study were:
• What was the effect of taking ALKS 3831 treatment for a long time on the severity of the participant’s mental health illness?
• Did taking ALKS 3831 change the participants’ feelings about how their weight impacts their overall well-being?
• How long did participants take ALKS 3831 during the study until they stopped taking it for any reason?
• What side effects did participants have during the study?
What treatment is being studied?
ALKS 3831 (also known as Lybalvi®) is a medication created from combining olanzapine and samidorphan. This medication is taken by mouth (oral).
• Olanzapine is an antipsychotic medication. Antipsychotic medications restore the balance of certain natural substances in the brain. By doing so, it helps reduce the symptoms of mental health illnesses like schizophrenia and bipolar disorder.
• Samidorphan is taken together with olanzapine. It helps reduce weight gain associated with olanzapine. Samidorphan does not affect the antipsychotic effects of olanzapine.
In May 2021, the United States health agency authorized ALKS 3831 to treat schizophrenia and/or bipolar I disorder in adults.
Who took part in this study?
This study included participants with schizophrenia, schizophreniform disorder, or bipolar I disorder.
People could take part in the study if they:
completed ALKS 3831 treatment in other clinical trials for ALKS 3831 within 7 days before joining this study AND had the potential to benefit from ALKS 3831 in the opinion of the study doctors People could not take part in the study if they:
had certain other health problems OR tested positive for drugs of abuse Of the 524 participants who joined the study, 523 took at least 1 dose of ALKS 3831.
• There were 322 (61.6%) male and 201 (38.4%) female participants.
• Participants were 16 to 68 years old. The average age was 35 years.
• A total of 188 (35.9%) participants finished the treatment period, and 335 (64.1%) did not finish the treatment period.
Among those who did not finish the treatment period, the most common reason was that participants chose to leave the study before it was over.
The sponsor ran this study at 98 locations in 13 countries. Some study sites did not have any participants signed up.
How was this study done?
Participants who completed ALKS 3831 treatment in other clinical trials within 7 days before starting this study were screened. They took the same dose of ALKS 3831 that they were taking at the end of their previous clinical trial.
ALKS 3831 was available in 4 doses:
• ALKS 3831 5/10: 5 milligrams (mg) olanzapine + 10 mg samidorphan • ALKS 3831 10/10: 10 mg olanzapine + 10 mg samidorphan • ALKS 3831 15/10: 15 mg olanzapine + 10 mg samidorphan • ALKS 3831 20/10: 20 mg olanzapine + 10 mg samidorphan This was an “open-label study.” This means that participants and study doctors knew that participants were taking ALKS 3831.Participants were to have health checks at the study site one time every month during the treatment period. The study doctors and staff at the study site kept track of the participants’
health and asked them how they were feeling.
One month after taking the last dose of ALKS 3831, participants were to return to the study site for a follow-up check-up.
The participants were in the study for up to 49 months.
When was this study done?
The study started on 15 June 2017 and ended on 06 September 2023.
The entire study took about 6 years and 3 months to complete.
What were the results of this study?
What was the effect of taking ALKS 3831 treatment for a long time on the severity of the participant’s mental health illness?
To answer this question, researchers rated the severity of the participant’s mental health illness using a tool called Clinical Global Impressions-Severity (CGI-S) scale during this study.
Then, researchers checked how participants were doing after their continued treatment of ALKS 3831 in this study after they completed another clinical trial.
Researchers found that:
Most participants continued to have mild mental health illness after taking ALKS 3831 in this study.
This means that some participants maintained adequate response from continued ALKS 3831 treatment.
Researchers also checked how much the participants’ CGI-S score changed after taking ALKS 3831 for 48 months compared to before joining the study (at baseline).
• A negative change from baseline in CGI-S score means that the severity of the participant’s mental health illness improved.
• A positive change from baseline in CGI-S score means that the severity of the participant’s mental health illness did not improve or had worsened.
Researchers found that:
The severity of the participant’s mental health illness became less severe after taking ALKS 3831 in this study.
Compared to baseline:
• CGI-S score reduced by 0.18 after 24 months of taking ALKS 3831.
• CGI-S score reduced by 0.24 after 48 months of taking ALKS 3831.
Did taking ALKS 3831 change the participants’ feelings about how their weight impacts their overall well-being?
To answer this question, researchers checked the results of a questionnaire called Impact of Weight on Quality of Life-Lite (IWQOL-Lite). The IWQOL-Lite checked the impact of the participants’ weight to their overall well-being.
The participants answered this questionnaire. A higher score meant higher satisfaction.
Researchers found that:
The participants’ IWQOL-Lite scores were high at baseline and remained high throughout the study.
This means that participants were satisfied with the impact of their weight to their overall well-being during the study.
How long did participants take ALKS 3831 during the study until they stopped taking it for any reason?
Participants took ALKS 3831 during the study for up to 504 to 672 days before stopping treatment.
The most common reason why participants stopped taking the treatment was because they chose to leave the study before it was over.
What side effects did participants have during the study?
The study doctors recorded all the symptoms the participants had during the study.
Unexpected and typically unwanted effects of a study treatment are called “side effects”. These side effects may or may not be related to the study treatment.
“Serious side effects” are side effects that result to death, are life-threatening, need hospital care, cause disability or permanent damage, cause birth defects, or are considered medically important by the study doctor.
This section includes the results of 523 participants who took at least 1 dose of ALKS 3831.
What serious side effects did participants have during the study?
The most common serious side effects – reported by more than 1 participant – during this study were:
• Schizophrenia in 11 participants (2.1%).
• Anxiety in 2 participants (0.4%).
None of the serious side effects were considered by study doctors to be related to ALKS 3831 treatment.
One (1) participant committed suicide and died during the study. The study doctor did not consider this side effect to be related to ALKS 3831.
The most common side effects that study doctors considered related to ALKS 3831 treatment were weight gain (48 participants [9.2%]) and sleepiness (28 participants [5.4%]).
How has this study helped researchers and patients?
You have helped us learn if ALKS 3831 may help treat schizophrenia or bipolar I disorder and if ALKS 3831 is safe to take for a long time.
This summary includes only some of the main results from this one study. Other studies may have different results.REC name
East Midlands - Derby Research Ethics Committee
REC reference
18/EM/0062
Date of REC Opinion
19 Apr 2018
REC opinion
Further Information Favourable Opinion