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

Phase 2

Completed

• Conditions: Acromegaly
• Interventions: Drug: Paltusotine; Drug: Placebo

• Registration Number: NCT03792555
• Lead Sponsor: Crinetics Pharmaceuticals Inc.

Brief Summary

A Phase 2 double-blind, placebo-controlled, randomized withdrawal study is designed to evaluate the safety, efficacy, and pharmacokinetics of paltusotine (formerly CRN00808) in subjects with acromegaly that are responders to octreotide LAR or lanreotide depot.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-12-27
• Study First Submitted QC: 2019-01-01
• Study First Posted: 2019-01-03
• Study Start: 2019-03-11
• Primary Completion: 2020-07-15
• Study Completion: 2020-08-12
• Disposition First Submitted: 2021-07-13
• Results First Submitted: 2024-09-11
• Status Verified: 2025-03
• Results First Submitted QC: 2025-03-04
• Last Update Submitted: 2025-03-04
• Results First Posted: 2025-03-17
• Disposition First Posted: 2025-03-17
• Last Update Posted: 2025-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Male and female subjects 18 to 75 years of age
2. Confirmed diagnosis of acromegaly that is controlled on stable doses of octreotide LAR or lanreotide depot
3. Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, or using effective method(s) of birth control
4. Willing to provide signed informed consent

Exclusion Criteria

1. Treatment naïve acromegaly subjects
2. Prior treatment with paltusotine
3. 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.
4. History or presence of malignancy except adequately treated basal cell and squamous cell carcinomas of the skin within the past 5 years.
5. Use of any investigational drug within the past 30 days or 5 half-lives, whichever is longer
6. 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
7. History of alcohol or substance abuse in the past 12 months
8. Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this study
9. Cardiovascular conditions or medications associated with prolonged QT or those which predispose subjects to heart rhythm abnormalities.
10. Subjects with symptomatic cholelithiasis
11. 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
12. 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)
13. Subjects taking octreotide LAR at a dose higher than 40 mg or lanreotide depot at a dose higher than 120 mg
14. Subjects who usually take octreotide LAR or lanreotide depot less frequently than every 4 weeks (e.g. every 6 weeks or 8 weeks)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Paltusotine	Paltusotine	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Responder Criteria Was Based on the Mean of Two Consecutive Insulin-like Growth Factor-1 [IGF-1] Measurements ≤ULN at Week 13	13 Weeks	Proportion of subjects who meet responder criteria (based on the mean of two consecutive IGF-1 measurements ≤ upper limit of normal \[ULN\])

Secondary Outcome Measures

Name	Time	Method
Change in IGF-1 Levels	From Week 10 to Week 13	Change in IGF-1 levels between RWP Baseline/Week 10 and Week 13
Change in Growth Hormone (GH) Levels	From Week 8 to Week 13	Change in growth hormone levels between RWP Baseline/Week 8 and Week 13
Change in Total ASD Score Between RWP Baseline/Week 10 and Week 13	From Week 10 to Week 13	Measured by total Acromegaly symptom diary (ASD) score from W10-W13.; ASD is a sponsor-developed daily diary to assess important acromegaly symptoms from the patient perspective. It covers 7 symptoms (headache pain, joint pain, sweating, fatigue, weakness in legs, swelling, and numbness or tingling). Patients rate the severity of each experience in the past 24 hours on an 11-point numeric scale that ranges from 0 (no symptom) to 10 (worst symptom).; A weekly average ASD score is calculated for each item as the sum of the item responses for a specific item over the course of the study week divided by the number of days on which the item was completed.; The weekly average ASD total score is calculated by computing the sum of the weekly average item scores for the 7 items (total range from 0 to 70), where higher score = higher symptom severity.

Trial Locations

Locations (11)

General Hospital of Athens "Gennimatas"; 🇬🇷 Athens, Greece

Semmelweis University Faculty of Medicine; 🇭🇺 Budapest, Hungary

University of Pécs Medical School; 🇭🇺 Pécs, Hungary

The Research Institute of Dallas; 🇺🇸 Dallas, Texas, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

CETI - Centro de Estudos em Terapias Inovadoras; 🇧🇷 Curitiba, Brazil

CPQuali Pesquisa Clinica; 🇧🇷 São Paulo, Brazil

Endocrine, Diabetes and Research Centre, Wellington Hospital; 🇳🇿 Wellington, New Zealand

The Centre of Postgraduate Medical Education; 🇵🇱 Warsaw, Poland

Clinical Centre Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases; 🇷🇸 Belgrade, Serbia

National Institute of Endocrinology and Diabetology; 🇸🇰 Ľubochňa, Slovakia