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 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 | 16.1 |
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 determine the effect of Octreolin therapy on Insulin-like Growth Factor 1 (IGF-1) levels and Growth Hormone (GH) levels, as measures of
response |
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E.2.2 | Secondary objectives of the trial |
1. To determine the effect of Octreolin therapy on IGF-1 levels and Growth Hormone (GH) levels
2. To assess the safety and tolerability of Octreolin in subjects with acromegaly
3. To compare the effect of Octreolin therapy on IGF-1 levels with that of injections with somatostatin analogs
Other objectives include:
1. To assess treatment satisfaction with injected vs. oral somatostatin analog therapy
2. To assess the rate of subjects who need to return to injectable therapy
3. Determine the PK profile of Octreolin during long term treatment |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic Sub-Study
Determine the PK profile of Octreolin during chronic treatment
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E.3 | Principal inclusion criteria |
1. Adult subjects, aged 18 to 75 years old, inclusive, at screening visit
2. Subjects with acromegaly defined as documented evidence of GH-secreting pituitary tumor that is abnormally responsive to glucose who are currently receiving regular parenteral injections at a stable dose for at least 3 months and are considered complete responders or at least partial responders to a somatostatin analog:
o Eligible somatostatin analogs includes: octreotide (sc and LAR), lanreotide (LA, Autogel or Depot)
o Complete response is defined as: IGF-1 normalized for age and integrated GH response over 2 hours < 2.5 ng/mL
o Partial response is defined as: IGF-1 < 30% above level normalized for age (i.e., < 1.3 times the upper limit of normal) and integrated GH response over 2 hours < 2.5 ng/mL
o Age-normalized IGF-1 will be considered the 2.5th to 97.5th percentile range for the central reference laboratory. Local laboratory values will not be used to qualify patients for the study
o Subjects taking regular injections of somatostatin analogs less frequently than monthly will not be eligible
o Subjects taking injections of octreotide on an as-needed basis to treat headaches will not be eligible
3. Subjects receiving appropriate stable doses of hormone replacement therapy for ≥3 months
4. Subjects able and willing to comply with the requirements of the protocol
5. Subjects able to swallow capsules
6. Subjects able to understand and sign written informed consent to participate in the study |
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E.4 | Principal exclusion criteria |
1. Symptomatic cholelithiasis
2. Received pituitary radiotherapy within ten years prior to screening
3. Undergone pituitary surgery within the prior 6 months
4. High-risk pattern of pituitary tumor location on pituitary MRI
5. Clinically significant GI, renal or hepatic disease as determined by the Principal Investigator. Conditions significantly affecting gastric acidity or emptying will typically exclude patients (e.g., bariatric surgery). Current use (within 1 month) of proton pump inhibitors (PPIs) and current chronic use of H2-antagonists will exclude subjects
6. Known allergy or hypersensitivity to any of the test compounds or materials.
7. Life expectancy of less than 2 years
8. Uncontrolled diabetes defined as having a fasting glucose > 150 mg/dL (8.3 mmol/L) or HbA1c ≥ 8% (Patients can be rescreened after diabetes is brought under adequate control); For Afro-Caribbeans, Fructosamine (marker of glucose tolerance) level of >288 mmol/L
9. Defects in visual fields due to optic chiasmal compression or other neurological signs, related to the pituitary tumor mass. Subjects with long-standing (>12 months), fixed, minor defects may be considered on a case-by-case basis after consultation with the Medical Monitor.
10. Active, clinically significant cardiac disease, including sustained arrhythmia, at time of screening
11. History of unstable angina or acute myocardial infarction within the three months preceding study screening
12. Female patients who are pregnant or lactating
13. Female patients who are of childbearing potential with a positive pregnancy test at screening or baseline or who not practicing an acceptable method for birth control. Acceptable methods include intrauterine devices, mechanical methods (e.g., vaginal diaphragm, vaginal sponge or condom with spermicidal jelly), or a vasectomized partner. Oral contraceptives are not permitted. Women may be surgically sterile or at least 1 year post-last menstrual period
14. History of immunocompromise, including a positive HIV test result (ELISA and Western blot)
15. Undergone major surgery/surgical therapy for any cause within 4 weeks prior to enrollment
16. Hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or steroid hormone replacement therapy for ≥ 3 months
17. History of alcohol or drug abuse
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. Intake of an investigational drug within 30 days before patient inclusion in this study
20. Current or recent (< 3 months) therapy with pegvisomant
21. Current or recent (< 2 months) therapy with cabergoline |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the concentrations of IGF-1 and mean GH over 2 hours at the end of the Core Treatment Period. |
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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) |
Proportion of patients with the following IGF-1 and GH values at baseline and end of Core Treatment Period:
o IGF-1 <1.3*ULN and GH <5 ng/mL
o IGF-1 <1.3*ULN and GH <1 ng/mL
o IGF-1 ≤1.0*ULN and GH <5 ng/mL
o IGF-1 ≤1.0*ULN and GH <2.5 ng/mL
o IGF-1 ≤1.0*ULN and GH <1 ng/mL
o IGF-1 <1.3*ULN
o IGF-1 ≤1.0*ULN
o GH <5ng/ml
o GH <2.5ng/ml
o GH <1 ng/mL
o IGF-1 ≥1.3 *ULN and GH <2.5 ng/mL
o GH ≤2.5 and IGF-1 <1.3*ULN
o IGF-1 ≥1.3*ULN and GH ≥2.5 ng/mL
•Proportion of subjects with IGF-1 levels (adjusted for age) <1.3*ULN at the end of the Core Treatment Period who also had IGF-1 levels (adjusted for
age) <1.3*ULN at the first assessment in the fixed dose period.
•Proportion of responders (IGF-1 levels [adjusted for age] <1.3*ULN and integrated GH <2.5) at the end of the Core Treatment Period who also had
IGF-1 levels (adjusted for age) <1.3*ULN and GH <2.5 at the first assessment in the fixed dose period. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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.8.1.7.1 | Other trial design description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 24 |
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 |
Italy |
Netherlands |
Romania |
Slovakia |
Germany |
Hungary |
Lithuania |
Israel |
Mexico |
Poland |
Slovenia |
United Kingdom |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |