E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acromegaly is typically caused by a growth hormone (GH) secreting tumor in the pituitary. Excess GH secretion results in excess secretion of insulin-like growth factor-1 (IGF-1) from the liver, which causes bone overgrowth, organ enlargement, and changes in glucose and lipid metabolism. The symptoms of acromegaly include abnormal growth of hands and feet and changes in shape of the bones that result in alteration of facial features. |
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E.1.1.1 | Medical condition in easily understood language |
Acromegaly is a chronic metabolic disorder in which there is too much growth hormone and the body tissues gradually enlarge. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000599 |
E.1.2 | Term | Acromegaly |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is designed to evaluate the long-term safety and tolerability of paltusotine in acromegaly subjects; to evaluate the efficacy of paltusotine in acromegaly patients. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completed one of the parent studies (Acrobat Evolve (CRN00808-02) or Acrobat Edge (CRN00808-03)) 2. Females must be non-pregnant and non-lactating either surgically sterile, post-menopausal, or using effective method(s) of birth control 3. Willing to provide signed informed consent |
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E.4 | Principal exclusion criteria |
1. Clinically significant concomitant disease including, but not limited to, cardiovascular disease; moderate or severe renal insufficiency; or significant liver disease (including cirrhosis) 2. Pituitary radiation since completing participation in parent studies 3. History or presence of malignancy except adequately treated basal cell and squamous cell carcinomas of the skin within the past 5 years 4. Positive test at Screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab). 5. History of alcohol or substance abuse in the past 12 months 6. Use of any investigational drug (other than paltusotine) within the past 30 days or 5 half-lives, whichever is longer before Screening 7. Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this study. 8. Cardiovascular conditions or medications associated with prolonged QT or those which predispose subjects to heart rhythm abnormalities 9. Subjects with symptomatic cholelithiasis 10. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: The primary endpoint is the incidence of treatment-emergent AEs (TEAEs) throughout the study.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints: -Change from the W16 visit (15 weeks of study treatment) in IGF-1 levels; -Change from W16 in growth hormone (GH) levels; Exploratory Endpoints: -Proportion of subjects with IGF-1 measurements ≤ULN at W52 each post-baseline visit; -Proportion of subjects with IGF-1 measurements ≤1.3×ULN at each post-baseline visit; -Proportion of subjects who achieve serum GH <5.0 ng/mL; -Proportion of subjects who achieve serum GH <2.5 ng/mL; -Number of consecutive visits with IGF-1 ≤ULN; -Number of consecutive visits with IGF-1 ≤1.3×ULN; - Increase in serum GH, IGF-1 levels after withdrawal of paltusotine; - Change from baseline in Acromegaly Quality of Life (AcroQoL) total score; - Change from baseline in acromegaly symptom diary (ASD total) score. - Subject treatment preference, as assessed by the Treatment Preference Questionnaire at W52;
Other Safety Endpoints: - Clinical laboratory tests (hematology, serum chemistry, and urinalysis) at each post-baseline study visit; - Vital signs at each post-baseline study visit; - 12-lead ECG at each post-baseline study visit. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Specific time points are given in E.5.2 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Serbia |
United Kingdom |
United States |
Germany |
Greece |
Hungary |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |