A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Evolve)

Study Overview
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Brief Summary
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A Phase 2 double-blind, placebo-controlled, randomized withdrawal study is designed to evaluate the safety, efficacy, and pharmacokinetics of paltusotine (formerly CRN00808; an oral selective nonpeptide somatostatin receptor type 2 biased agonist) in subjects with acromegaly that are responders to octreotide LAR or lanreotide depot.

Official Title
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A Double-blind, Placebo-controlled, Randomized Withdrawal Study to Evaluate the Safety, Pharmacokinetics and Efficacy of CRN00808 in Patients With Acromegaly That Are Responders to Octreotide LAR or Lanreotide Depot (ACROBAT Evolve)

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Paltusotine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects 18 to 70 years of age Confirmed diagnosis of acromegaly that is controlled on stable doses of octreotide LAR or lanreotide depot Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, or using effective method(s) of birth control Willing to provide signed informed consent Exclusion Criteria: Treatment naïve acromegaly subjects Prior treatment with paltusotine Pituitary surgery within 6 months prior to Screening or radiation therapy at any time prior to the study entry. Pituitary radiation therapy (within 3 to 4 years or more than 4 years prior to study entry) with recently documented elevated IGF-1 may be eligible. History or presence of malignancy except adequately treated basal cell and squamous cell carcinomas of the skin within the past 5 years. Use of any investigational drug within the past 30 days or 5 half-lives, whichever is longer Positive test at Screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab) or has a history of a positive result History of alcohol or substance abuse in the past 12 months Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this study Cardiovascular conditions or medications associated with prolonged QT or those which predispose subjects to heart rhythm abnormalities. Subjects with symptomatic cholelithiasis Subjects with clinically significant abnormal findings during the Screening Period, and any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the subject's safety or ability to complete the study Subjects who have been taking the following prior medications: pegvisomant (within the last 3 months), dopamine agonists (within the last 3 months) and pasireotide LAR (within the last 6 months) Subjects taking octreotide LAR at a dose higher than 40 mg or lanreotide depot at a dose higher than 120 mg Subjects who usually take octreotide LAR or lanreotide depot less frequently than every 4 weeks (e.g. every 6 weeks or 8 weeks)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paltusotine<br> | Drug: Paltusotine<br>* Paltusotine, capsules, once daily by mouth<br>* Other names: CRN00808;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo, capsules, once daily by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who meet responder criteria (based on the mean of two consecutive insulin-like growth factor-1 [IGF-1] measurements ≤ upper limit of normal [ULN]) |  | 13 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IGF-1 levels |  | From Week 10 to Week 13 | 
| Change in growth hormone (GH) levels |  | From Week 8 to Week 13 | 
| Change in patient assessed symptoms of acromegaly | Total score computed by adding each of the individual acromegaly symptom intensities (headache pain, joint pain, sweating, fatigue, weakness in legs, swelling, numbness or tingling). | From Week 10 to Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acromegaly, ACROBAT, EVOLVE, Paltusotine