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 a hormonal disorder mainly resulting from a tumor in the pituitary gland, leading to excess of growth hormone |
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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 assess maintenance of biochemical control with octreotide capsules compared to placebo in patients with acromegaly, who previously demonstrated biochemical control on SRLs |
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E.2.2 | Secondary objectives of the trial |
_To assess maintenance of biochemical control, based on GH, with octreotide capsules compared to placebo.
_To evaluate the safety profile of octreotide capsules compared to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult subjects, aged ≥18 years old at the first Screening visit.
2. Patients with active acromegaly, defined as documented evidence of GH-secreting pituitary tumor based on MRI/Pathology report and documented evidence of IGF-1 levels ≥1.3 × ULN. This needs to be at least 3 months following pituitary surgery in
those patients who had prior pituitary surgery.
3. Received parenteral SRL monotherapy (octreotide or lanreotide but not pasireotide) for at least 6 months with a stable dose for at least the last three months of therapy.
4. Average IGF-1 of 2 assessments obtained during the Screening period is ≤1 * ULN.
5. Patients able and willing to comply with the requirements of the protocol at the time of Screening.
6. Women who are of childbearing potential should use an acceptable method for birth control. Acceptable methods include hormonal contraception (oral contraceptives – as long as on stable dose, patch, implant, and injection), intrauterine devices, or double
barrier methods (e.g. vaginal diaphragm/ vaginal sponge plus condom, or condom plus spermicidal jelly), sexual abstinence or a vasectomized partner. Women may be surgically sterile or at least 1-year post-last menstrual period. Women taking oral contraception containing levonorgestrel should either change treatment (at least one month prior to first study medication dose) or use a mechanical barrier method.
7. Patients able to understand and sign written informed consent to participate in the study. |
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E.4 | Principal exclusion criteria |
1. Patients taking injections of long-acting SRLs off label (unlabeled doses or dosing interval. e.g. 60 or 90 mg lanreotide every 8 weeks or 30 mg octreotide every 6 or 8 weeks).
2. Patients who previously participated in CH-ACM-01 or OOC-ACM-302 (MPOWERED).
3. Symptomatic cholelithiasis.
4. Conventional or stereotactic Radiotherapy any time in the past.
5. Undergone pituitary surgery within six months prior to screening or have elective pituitary surgery (or other elective surgery that may affect compliance with protocol or confound study outcomes), planned within the course of the core study.
6. High-risk pattern of pituitary tumor location on pituitary magnetic resonance imaging (MRI)/Computed tomography (CT) as per medical history or most recent MRI/CT.
7. History of unstable angina or acute myocardial infarction within the 12 weeks preceding the screening visit or other clinically significant cardiac disease at the time of screening as judged by the Principal Investigator.
8. Any clinically significant uncontrolled nervous system, gastrointestinal (GI), renal, pulmonary, or hepatic concomitant disease that in the Investigator’s opinion would preclude patient participation.
9. Evidence of active malignant disease or malignancies diagnosed within the previous one year (except for basal cell carcinoma and uncomplicated – up to stage 1 squamous cell carcinoma that has been excised and cured).
10. Known allergy or hypersensitivity to any of the test compounds or materials.
11. Known uncontrolled diabetes defined as having a fasting glucose > 150 mg/dL (8.3 mmol/L) or glycosylated hemoglobin (HbA1c) ≥ 8% (patients can be rescreened after diabetes is brought under adequate control, or in case HbA1c < 8%).
12. Known defects in visual fields due to optic chiasmal compression or other neurological signs, related to the pituitary tumor mass. Patients with long-standing (>12 months), fixed, minor defects may be considered on a case-by-case basis after consultation with the
medical monitor.
13. Female patients who are pregnant or lactating or intending to become pregnant during the study.
14. Known history of immunodeficiency (e.g., HIV positive).
15. ALT, AST or ALP > 3 * ULN or Total Bilirubin >1.5 * ULN.
16. Undergone major surgery/surgical therapy for any cause within four weeks prior to enrollment or planned procedure during the study.
17. Known hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or steroid hormone replacement therapy for ≥ 12 weeks.
18. Any condition that may jeopardize study participation (e.g., clinically significant abnormal screening clinical or laboratory finding during screening), the interpretation of study results or may impede the ability to obtain informed consent (e.g., mental condition).
19. History of illicit drug or alcohol abuse within five years.
20. Intake of an investigational drug within 30 days prior to initiation of study treatment.
21. Treatment with pegvisomant within 24 weeks before the first screening visit.
22. Treatment with dopamine agonists within 12 weeks before the screening visit.
23. Treatment with pasireotide within 24 weeks before the first screening visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients who maintain their biochemical response at the end of the DPC period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Maintenance of response will be defined by using the average IGF-1 level of the last 2 available assessments between weeks 34 and 36 in the DPC period. If the average IGF-1 is ≤ 1 × ULN, a patient will be classified as a responder (i.e., maintained their biochemical response). If the average IGF-1 is > 1 × ULN, a patient will be classified as a non-responder. Patients who discontinue study
medication during the DPC period for any reason will be classified as nonresponders for the primary analysis, regardless of their IGF-1 values. |
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E.5.2 | Secondary end point(s) |
_Proportion of patients who maintain GH response (i.e., GH < 2.5 ng/mL) at week 36, out of those who were responders (i.e., GH < 2.5 ng/mL) on SRL injections at Screening. GH response will be defined using the mean integrated GH value, based on 5 assessments, 30 minutes apart. Patients who discontinue treatment during the DPC period for any reason will be classified as non-responders, regardless of their IGF-1 values.
_Time to loss of response: Loss of response is defined as the earliest time when the IGF-1 of 2 consecutive visits is > 1×ULN, after the patient is treated for at least 2 weeks with 4 capsules per day.
_Time to loss of response: Loss of response is defined as the earliest time when the IGF-1 of 2 consecutive visits is > 1.3×ULN, after the patient is treated for at least 2 weeks with 4 capsules per day
_Proportion of patients who begin rescue treatment prior to and including week 36. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline from end of treatment |
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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 | No |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
Bulgaria |
Canada |
Denmark |
Germany |
Hungary |
Israel |
Italy |
Latvia |
Netherlands |
Poland |
Romania |
Slovenia |
Sweden |
Turkey |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |