Efficacy and Safety of Octreotide (MYCAPSSA™ [Formerly Octreolin™]) for Acromegaly

Study Overview
=================
Brief Summary
-----------------
MYCAPSSA™ (formerly Octreolin™) is a proprietary oral form of the approved injectable medical product octreotide used to treat acromegaly. This study will evaluate the efficacy and safety of MYCAPSSA™ treatment in patients with acromegaly.

Detailed Description
-----------------
The study consisted of 2 periods, a Core Treatment Period of up to 7 months and an optional Extension Treatment Period of up to 6 months, for a total study duration of up to 13 months. The Core Treatment Period consisted of 2 phases, a Dose Escalation Phase of at least 2 months to identify the therapeutic dose for each study participant and a Fixed Dose Phase of 2 to 5 months during which the therapeutic dose was maintained. Participants were eligible to enter the Fixed Dose Phase of the Core Treatment Period if they were clinically and biochemically controlled. The same criteria were used to allow entry into the voluntary 6-month Extension Treatment Period. The Core Treatment Period of the study was completed if the participant had at least 2 months of treatment in the Fixed Dose Phase and a total treatment duration of at least 7 months. Participants who elected to continue into the Extension Treatment Period maintained their therapeutic dose during this period. At the end of the study (after the last dose of MYCAPSSA in either the Core Treatment Period or the Extension Treatment Period), there was a 2-week follow-up period for safety assessments.

Official Title
-----------------
Efficacy and Safety of Oral Octreolin™ in Patients With Acromegaly Who Are Currently Receiving Parenteral Somatostatin Analogs

Conditions
-----------------
Acromegaly

Intervention / Treatment
-----------------
* Drug: Octreotide capsules


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult subjects, aged 18 to 75 years old, inclusive. Subjects with acromegaly defined as documented evidence of growth hormone-secreting pituitary tumor that is abnormally responsive to glucose, or documented elevated insulin-like growth factor-1 (IGF-1), who are currently receiving a stable dose of a somatostatin analog for at least the previous 3 months. A serum IGF-1 level < 1.3 x the upper limit of normal (ULN) and a serum growth hormone (GH) level < 2.5 ng/mL. Subjects able and willing to comply with the requirements of the protocol. Subjects able to swallow capsules. Subjects able to understand and sign written informed consent to participate in the study. Exclusion Criteria: Receiving regular injections of a somatostatin analog less frequently than once a month, ie, longer than every 4 weeks. Symptomatic cholelithiasis. Received pituitary radiotherapy within ten years prior to screening. Undergone pituitary surgery within the prior 6 months. Any condition that may jeopardize study participation. Clinically significant gastrointestinal (GI), renal, or hepatic disease as determined by the Investigator. Conditions (eg, bariatric surgery) significantly affecting gastric acidity or emptying. Current use (within 1 month) of proton pump inhibitors (PPIs) and current chronic use of H2-antagonists. Female patients who are pregnant or lactating. Current or recent (< 3 months) therapy with pegvisomant. Current or recent (< 2 months) therapy with cabergoline.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Octreotide capsules<br>Participants received octreotide capsules orally twice a day for up to 13 months. Dosing started at 40 mg per day (20 in the morning + 20 in the evening) and increased to 60 mg per day (40 in the morning + 20 in the evening) or 80 mg per day (40 in the morning + 40 in the evening) if there was inadequate IGF-1 suppression. | Drug: Octreotide capsules<br>* Octreotide was provided in hard gelatin capsules.<br>* Other names: Formerly known as Octreolin™;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders at the End of the Core Treatment Period | A responder was defined as a participant with a serum insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal (adjusted for age and gender) and a growth hormone (GH) concentration < 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed. | End of the core treatment period (up to 7 months) | 
| Percentage of Responders at the End of the Extension Treatment Period | A responder was defined as a participant with a serum insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal (adjusted for age and gender) and a growth hormone (GH) concentration < 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed. | End of the extension treatment period (up to 13 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period | Percentage of participants with the following serum insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations at Baseline and at the end of the core treatment period (ECTP): IGF-1 < 1.3 times the upper limit of normal (ULN) and GH < 5.0 ng/mL, IGF-1 < 1.3 times ULN and GH < 1.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 5.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 2.5 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 1.0 ng/mL, IGF-1 < 1.3 times ULN, IGF-1 ≤ 1.0 times ULN, GH < 5.0 ng/mL, GH < 2.5 ng/mL, GH < 1.0 ng/mL, IGF-1 ≥ 1.3 times ULN and GH < 2.5 ng/mL, IGF-1 < 1.3 times ULN and GH ≥ 2.5 ng/mL, and IGF-1 ≥ 1.3 times ULN and GH ≥ 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed. | Baseline and the end of the core treatment period (up to 7 months) | 
| Maintenance of Response During the Fixed Dose Phase of the Core Treatment Period | Maintenance of response during the fixed dose phase of the core treatment period was defined as the percentage of participants with an insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal at the beginning of the fixed dose phase of the core treatment period and at the end of the core treatment period. IGF-1 concentration was determined in serum samples taken at the same visits growth hormone concentration was assessed. | Beginning of the fixed dose phase of the core treatment period and the end of the core treatment period (up to 7 months) | 
| Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period | Percentage of participants with the following serum insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations at the beginning (BETP) and at the end (EETP) of the extension treatment period: IGF-1 < 1.3 times the upper level of normal (ULN) and GH < 5.0 ng/mL, IGF-1 < 1.3 times ULN and GH < 1.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 5.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 2.5 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 1.0 ng/mL, IGF-1 < 1.3 times ULN, IGF-1 ≤ 1.0 times ULN, GH < 5.0 ng/mL, GH < 2.5 ng/mL, GH < 1.0 ng/mL, IGF-1 ≥ 1.3 times ULN and GH < 2.5 ng/mL, IGF-1 < 1.3 times ULN and GH ≥ 2.5 ng/mL, and IGF-1 ≥ 1.3 times ULN and GH ≥ 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed. | Beginning and the end of the extension treatment period (up to 6 months) | 
| Maintenance of Response During the Extension Treatment Period | Maintenance of an insulin-like growth factor-1 (IGF-1) response during the extension treatment period was defined as the percentage of participants with an IGF-1 concentration < 1.3 times the upper limit of normal at the beginning of the extension treatment period and at the end of the extension treatment period. IGF-1 concentration was determined in serum samples taken at the same visits growth hormone concentration was assessed. | Beginning of the extension treatment period and the end of the extension treatment period (up to 13 months) | 
| Percentage of Participants With Improved or Maintained Acromegaly Symptoms at the End of the Extension Treatment Period | The severity (absent, mild, moderate, severe) of the 5 acromegaly symptoms headache, perspiration, asthenia, swelling of extremities, and joint pain was assessed at Baseline and at the end of the extension treatment period. The percentage of participants with improved or maintained (no change) acromegaly symptoms from Baseline at the end of the extension treatment period is reported. | Baseline and the end of the extension treatment period (up to 13 months) | 
| Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period | Reported is the percentage of participants who had ≥ 1, 2, or 3 of the 5 symptoms of acromegaly (headaches, perspiration, asthenia, swelling of extremities, or joint pain) of any severity (mild, moderate, or severe). This was a post hoc analysis. | Baseline and the end of the extension treatment period (up to 13 months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
acromegaly, IGF-1, growth hormone, Octreolin, octreotide, somatostatin analog