E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Acromegaly is typically caused by a growth hormone (GH) secreting tumor in the pituitary. |
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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 |
To evaluate the effect of paltusotine versus placebo on IGF-1 response |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of paltusotine versus placebo on IGF-1 level To evaluate the effect of paltusotine versus placebo on GH response To evaluate the effect of paltusotine versus placebo on acromegaly symptoms. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male and female subjects ≥18 years of age 2.Confirmed diagnosis of acromegaly and controlled (as measured by IGF-1 ≤1.0×ULN) via stable monotherapy dose of protocol defined somatostatin receptor ligand therapy. (Upper limit of eligibility is mean IGF-1 of 1.04 rounded to 2 decimal places.) 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. |
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E.4 | Principal exclusion criteria |
1.Treatment naïve acromegaly subjects 2.Prior treatment with paltusotine. 3. History of pituitary radiation therapy. 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.Known history of HIV, hepatitis B, or active hepatitis C. 7.History of alcohol or substance abuse in the past 12 months. 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, or 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 11.Subjects currently taking pasireotide LAR (within 24 weeks prior to Screening) or pegvisomant, dopamine agonists, or short acting somatostatin analogs (with 12 weeks prior to Screening) |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Proportion of subjects who maintain biochemical response in IGF-1 (≤1.0×the upper limit of normal [ULN]) at the End of the Randomized Control Phase (EOR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
36 weeks for the primary endpoint. |
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E.5.2 | Secondary end point(s) |
•Change from baseline in IGF-1, in units of ULN, to EOR •Proportion of subjects with GH <1.0 ng/mL at Week 34, out of those who had GH <1.0 ng/mL at Screening •Change from baseline in Total Acromegaly Symptoms Diary (ASD) score to EOR. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
36 weeks for the secondary endpoint. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 9 |
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 |
Argentina |
Peru |
Brazil |
Israel |
Russian Federation |
Serbia |
United Kingdom |
United States |
Austria |
Belgium |
Bulgaria |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Last visit of the last subject in the study |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 |