E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
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 |
|
E.2.2 | Secondary objectives of the trial |
To determine the effect of Octreolin therapy on IGF-1 levels and Growth
Hormone (GH) levels
To assess the safety and tolerability of Octreolin in subjects with
acromegaly |
|
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 |
|
E.3 | Principal inclusion criteria |
1.Adult subjects, aged 18 to 75 years old, inclusive, at screening visits
2.Subjects with acromegaly defined as documented evidence of GHsecreting
pituitary tumor that is abnormally responsive to glucose who
are currently receiving somatostatin analog.
3.Subjects able and willing to comply with the requirements of the
protocol
4.Subjects able to swallow capsules
5.Subjects able to understand and sign written informed consent to
participate in the study |
|
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.Clinically significant GI, renal or hepatic disease.
5.Known allergy or hypersensitivity to any of the test compounds or
materials
6.Life expectancy of less than 2 years
7.Uncontrolled diabetes
8.Defects in visual fields due to optic chiasmal compression
9.Female patients who are pregnant or lactating
10.Female patients who are of childbearing potential
11.History of immunocompromise, including a positive HIV test result
(ELISA and Western blot)
12.History of alcohol or drug abuse
13.Intake of an investigational drug within 30 days before patient
inclusion in this study |
|
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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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.8.2 | 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 |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Serbia |
Slovenia |
United Kingdom |
United States |
|
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
|
|
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 | 7 |
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 |