Acromegaly
Conditions
Keywords
Octreotide Capsules, Acromegaly, OPTIMAL, MYCAPSSA
Brief summary
Octreotide capsule is a novel, orally-administered formulation of the commercially-available injectable drug octreotide. In a recent phase 3 trial, oral octreotide capsules demonstrated maintenance of biochemical response up to 13 months in the majority of patients with acromegaly previously managed with somatostatin analog injections (reference below).
Detailed description
This is a double blind, randomized study that assesses the efficacy and safety of octreotide capsules vs. placebo. Eligible acromegaly patients, treated with injectable somatostatin analogs, who are biochemically controlled and have prior evidence of active disease, will be randomized to receive either octreotide capsules or placebo for up to 36 weeks. At the end of this double blind, placebo controlled period, eligible patients will receive octreotide capsules in an open-labeled extension for at least one year. Patients failing to respond (per protocol), to oral treatment, (either placebo or octreotide capsules), will be rescued with the standard of care and upon meeting the eligibility criteria could also enroll into the long term extension with octreotide capsules. This study received agreement from the FDA, under a special protocol assessment.
Interventions
octreotide capsules 40 mg/day, 60 mg/day, 80 mg/day (individual dose titration)
DRUGMatching placebo
Matching placebo capsules
Sponsors
Chiasma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented evidence of active acromegaly * Treatment with Somatostatin analogs injections (octreotide or lanreotide) for at least 6 months with a stable dose for at least the last three months of therapy * Biochemically controlled
Exclusion criteria
* Patients taking injections of long-acting Somatostatin Receptor Ligands (SRLs) not as indicated in the label * Pituitary surgery within six months * Conventional or stereotactic pituitary radiotherapy any time in the past * Patients who previously participated in CH-ACM-01 or OOC-ACM-302 * Any clinically significant uncontrolled concomitant disease * Symptomatic cholelithiasis * Pegvisomant, within 24 weeks * Dopamine agonists, within 12 weeks * Pasireotide, within 24 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Maintain Their Biochemical Response at the End of the Double Blind Placebo Controlled (DPC) Period. | Week 36 | Maintenance of response was defined by using the average IGF-1 level of the last 2 available assessments in the DPC period. If the average IGF-1 is ≤ 1×ULN, a patient was classified as a responder (i.e., maintained their biochemical response). If the average IGF-1 is \> 1×ULN, a patient was classified as a non-responder. Patients who discontinue study medication during the DPC period for any reason was classified as non-responders for the primary analysis, regardless of their IGF-1 values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Maintain Growth Hormone (GH) Response at the End of the Double Blind Placebo Controlled Period | Week 36 | Maintenance of GH response was defined as having mean Growth Hormone (5 measurements 30 minutes apart) \< 2.5 ng/mL at the end of the double blind placebo controlled period, out of those who were responders on Somatostatin Receptor Ligands (SRLs) injections at Screening. |
| Number of Patients Who Begin Rescue Treatment | Week 36 | Number of Patients who Began Rescue Treatment Prior to and Including Week 36 |
Countries
Australia, Bulgaria, Canada, Denmark, Germany, Hungary, Israel, Italy, Latvia, Netherlands, New Zealand, Poland, Slovenia, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Octreotide Capsules Octreotide capsules
octreotide capsules: octreotide capsules 40mg/day, 60mg/day, 80 mg/day (individual dose titration) | 28 |
| Matching Placebo Matching placebo capsules
Matching placebo: Matching placebo capsules | 28 |
| Total | 56 |
Baseline characteristics
| Characteristic | Total | Octreotide Capsules | Matching Placebo |
|---|---|---|---|
| Age, Continuous Age | 54.7 years STANDARD_DEVIATION 11.38 | 55.3 years STANDARD_DEVIATION 11.97 | 54.2 years STANDARD_DEVIATION 10.96 |
| Baseline average Insulin-like Growth Factor 1 (IGF-1) (categorical) IGF≥ 1.3 ULN | 0 Participants | 0 Participants | 0 Participants |
| Baseline average Insulin-like Growth Factor 1 (IGF-1) (categorical) IGF > 1 to < 1.3 ULN | 6 Participants | 1 Participants | 5 Participants |
| Baseline average Insulin-like Growth Factor 1 (IGF-1) (categorical) IGF≤ 1 Upper Limit of Normal (ULN) | 50 Participants | 27 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 28 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 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 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 51 Participants | 27 Participants | 24 Participants |
| Sex: Female, Male Female | 30 Participants | 16 Participants | 14 Participants |
| Sex: Female, Male Male | 26 Participants | 12 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 28 / 28 | 27 / 28 |
| serious Total, serious adverse events | 2 / 28 | 1 / 28 |
Outcome results
Primary
Number of Patients Who Maintain Their Biochemical Response at the End of the Double Blind Placebo Controlled (DPC) Period.
Maintenance of response was defined by using the average IGF-1 level of the last 2 available assessments in the DPC period. If the average IGF-1 is ≤ 1×ULN, a patient was classified as a responder (i.e., maintained their biochemical response). If the average IGF-1 is \> 1×ULN, a patient was classified as a non-responder. Patients who discontinue study medication during the DPC period for any reason was classified as non-responders for the primary analysis, regardless of their IGF-1 values.
Time frame: Week 36
Population: Number of Patients who Maintained Their Biochemical Response at the End of the DPC Period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Octreotide Capsules | Number of Patients Who Maintain Their Biochemical Response at the End of the Double Blind Placebo Controlled (DPC) Period. | 16 Participants |
| Matching Placebo | Number of Patients Who Maintain Their Biochemical Response at the End of the Double Blind Placebo Controlled (DPC) Period. | 5 Participants |
Comparison: The proportion of \[IGF-1/GH\] responders was compared between treatment groups using an exact logistic regression model with categorical covariates for treatment group, prior SRL dose, and baseline \[IGF-1/GH\] levelp-value: 0.0079Regression, Logistic
Secondary
Number of Patients Who Begin Rescue Treatment
Number of Patients who Began Rescue Treatment Prior to and Including Week 36
Time frame: Week 36
Population: The number of patients who began rescue treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Octreotide Capsules | Number of Patients Who Begin Rescue Treatment | 7 Participants |
| Matching Placebo | Number of Patients Who Begin Rescue Treatment | 19 Participants |
p-value: 0.0029Fisher Exact
Secondary
Number of Patients Who Maintain Growth Hormone (GH) Response at the End of the Double Blind Placebo Controlled Period
Maintenance of GH response was defined as having mean Growth Hormone (5 measurements 30 minutes apart) \< 2.5 ng/mL at the end of the double blind placebo controlled period, out of those who were responders on Somatostatin Receptor Ligands (SRLs) injections at Screening.
Time frame: Week 36
Population: Number of patients who maintain Growth Hormone (GH) response at the end of the double blind placebo controlled period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Octreotide Capsules | Number of Patients Who Maintain Growth Hormone (GH) Response at the End of the Double Blind Placebo Controlled Period | 21 Participants |
| Matching Placebo | Number of Patients Who Maintain Growth Hormone (GH) Response at the End of the Double Blind Placebo Controlled Period | 7 Participants |
Comparison: The proportion of \[IGF-1/GH\] responders was compared between treatment groups using an exact logistic regression model with categorical covariates for treatment group, prior SRL dose, and baseline \[IGF-1/GH\] levelp-value: 0.0007Regression, Logistic