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

Acromegaly Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03792555
• Other study ID #: CRN00808-02
• Secondary ID: 2018-001833-42
• Status: Completed
• Phase: Phase 2
• Start date: December 18, 2018
• Est. completion date: August 12, 2020

Study information

• Verified date: July 2021
• Source: Crinetics Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: August 12, 2020
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Male and female subjects 18 to 70 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)

Related Conditions & MeSH terms

• Acromegaly

Intervention

Drug:
• Paltusotine
Paltusotine, capsules, once daily by mouth
• Placebo
Placebo, capsules, once daily by mouth

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Royal Brisbane & Women's Hospital	Herston
Australia	Royal Melbourne Hospital	Melbourne
Australia	Keogh Institute for Medical Research	Nedlands
Brazil	CETI - Centro de Estudos em Terapias Inovadoras	Curitiba
Brazil	Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ) Centro de Pesquisa em Neuroendocrinologia	Rio De Janeiro
Brazil	CPQuali Pesquisa Clinica	São Paulo
Germany	MEDICOVER Neuroendokrinologie	München
Germany	LMU Clinic of University of Munich	Munich
Greece	General Hospital of Athens "Evangelismos"	Athens
Greece	General Hospital of Athens "Gennimatas"	Athens
Greece	General Hospital of Athens "Laiko"	Athens
Greece	General Hospital of Athens "Ippokratio"	Thessaloníki
Hungary	Military Health Center, Division of Endocrinology	Budapest
Hungary	Semmelweis University Faculty of Medicine	Budapest
Hungary	University of Pécs Medical School	Pécs
Italy	Universita Vita-Salute San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
New Zealand	Waitemata District Health Board, North Shore Hospital	Takapuna
New Zealand	Endocrine, Diabetes and Research Centre, Wellington Hospital	Wellington
Poland	Clinic of Endocrinology Independent Public Health Care Centre University Hospital in Kracow	Krakow
Poland	Centrum Nowoczesnch Terapii "Dobry Lekarz"	Kraków
Poland	The Centre of Postgraduate Medical Education	Warsaw
Romania	National Institute of Endocrinology "C. I. Parhon"	Bucharest
Romania	Emergency Clinical County Hospital, Endocrinology Clinic	Cluj-Napoca
Serbia	Clinical Centre Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases	Belgrade
Serbia	Clinical Centre of Vojvodina, Clinic for Endocrinology, Diabetes and Metabolic Diseases	Novi Sad
Slovakia	University Hospital Bratislava	Bratislava
Slovakia	National Institute of Endocrinology and Diabetology	Lubochna
United Kingdom	University Hospitals Coventry and Warwickshire NHS Trust	Coventry
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Barts and the London School of Medicine	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Research Institute of Dallas	Dallas	Texas
United States	Keck Medical Center of USC University of Southern California	Los Angeles	California
United States	UCLA Gonda Diabetes Center	Los Angeles	California
United States	Allegheny Endocrinology Associates	Pittsburgh	Pennsylvania
United States	OHSU Northwest Pituitary Center	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Crinetics Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Germany,  Greece,  Hungary,  Italy,  New Zealand,  Poland,  Romania,  Serbia,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in IGF-1 levels		From Week 10 to Week 13
Secondary	Change in growth hormone (GH) levels		From Week 8 to Week 13
Secondary	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