E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acromegaly is characterized by chronic hypersecretion of growth hormone (GH), clinical features comprise structural and functional changes occurring in practically all organs. Cardiovascular disease is the main reason for morbidity and increased mortality. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.1 |
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 compare the proportion of patients achieving biochemical control defined as mean GH levels < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continuing the same treatment with octreotide LAR 30 mg or lanreotide ATG 120 mg. |
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E.2.2 | Secondary objectives of the trial |
Key Secondary: To compare the effect of pasireotide LAR (40mg and 60 mg seperately) versus continuing the same treatment on the proportion of patients achieving normalization of sex- and age-adjusted IGF-1 at 24 weeks.
Secondary:
To assess the effect of pasireotide LAR (40 mg and 60 mg separately) vs continuing the same treatment on the proportion of patients achieving:
•biochemical control defined as mean GH levels < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 12 weeks,
•GH levels < 2.5 µg/L at 12 and 24 weeks,
•normal, sex- and age-adjusted IGF-1 at 12 weeks,
•GH levels < 1 µg/L and normal, sex- and age-adjusted IGF-1 at 12 and 24 weeks,
•GH levels < 1 µg/L at 12 and 24 weeks,
•a tumor volume reduction > 25% assessed by pituitary MRI at 24 weeks,
see protocol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male and female patients ≥ 18 years of age
•Patients with written informed consent prior to any study related activity
•Patients with inadequately controlled acromegaly as defined by
•a mean GH concentration of a 5-point profile over a 2-hour period > 2.5 µg/L
and
•sex- and age adjusted IGF-1 > 1.3 x upper limit of normal (ULN)
•Patients treated with maximum indicated doses of octreotide LAR or lanreotide ATG for at least 6 months prior to Visit 1 (Screening). The maximum indicated dose for octreotide LAR is 30 mg and for lanreotide ATG is 120 mg
•Patients with diagnosis of pituitary micro- or macro adenoma. Patients can have been previously submitted to surgery
Additional inclusion criteria as per full protocol may apply |
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E.4 | Principal exclusion criteria |
1.Patients who have received pasireotide (SOM 230) prior to enrolment
2. Concomitant treatment with Growth Hormone Receptor (GHR)-
antagonist or dopamine agonists unless concomitant treatment was
discontinued 8 weeks prior to visit 1 (screening)(8 weeks wash out
period). Such patients must have been treated with octreotide LAR 30
mg or lanreotide ATG 120 mg monotherapy continuously for a minimum
of 6 months prior to starting combination therapy and they should have
been inadequately controlled on monotherapy.
3. Patients with compression of the optic chiasm causing acute clinically
significant visual field defects
4. Patients who require a surgical intervention for relief of any sign or
symptom associated with tumor compression
5. Patients who have received pituitary irradiation within 10 years prior
to visit 1 (screening).
6. Patients who have undergone major surgery/surgical therapy for any
cause within 4 weeks prior to visit 1 (screening).
7. Patients who are hypothyroid and not adequately treated with a stable
dose of thyroid hormone replacement therapy
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint
The proportion of patients with a reduction of mean GH levels to < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks
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E.5.2 | Secondary end point(s) |
The endpoint for the key secondary objective is:
• the proportion of patients achieving normalization of sex- and age-adjusted IGF-1 at 24 weeks.
The secondary end points are:
•the proportion of patients achieving biochemical control defined as mean GH levels < 2.5 μg/L and normalization of sex- and age-adjusted IGF-1 at 12 weeks,
•the proportion of patients achieving GH levels < 2.5 μg/L at 12 and 24 weeks,
•the proportion of patients achieving normal IGF-1 (sex- and age-adjusted) at 12 and 24 weeks,
•the proportion of patients achieving GH levels < 1 μg/L and normal, sex- and age-adjusted IGF-1 at 12 and 24 weeks,
•the proportion of patients achieving GH levels < 1 μg/L at 12 and 24 weeks,
•the proportion of patients achieving a tumor volume reduction > 25% assessed by pituitary MRI at24 weeks,
•the percent change in tumor volume assessed by pituitary MRI from baseline to 24 weeks,
•the change from baseline in clinical signs/symptoms of acromegaly (ring size; headache, fatigue, perspiration, paresthesias and osteoarthralgia according to a five-point score scale),
•the change from baseline in health related QoL as measured by the AcroQoL (acromegaly health related QoL)
Additional endpoint as per full protocol may apply |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary:
24 weeks
1. 12 weeks
2. 24 weeks
3. 12 and 24 weeks
4. 24 weeks
5. 24 weeks |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Brazil |
Israel |
Mexico |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |