E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 assess the efficacy of the co-administration of lanreotide Autogel 120 mg (administered via deep sub-cutaneous injections every 28 days) and pegvisomant (administered at 40 to 120 mg per week via sub-cutaneous injection given once or twice a week) on IGF-1 levels over 28 weeks in acromegalic patients. The primary endpoint will be the percentage of acromegalic patients with normalised (age and sex adjusted) IGF-1 level at the end of the co-treatment period.
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E.2.2 | Secondary objectives of the trial |
To assess the effect of lanreotide - pegvisomant co-administration on: • Acromegaly symptoms. • Quality of life. • Safety based on: - Adverse events, clinical examination, vital signs - Glucose tolerance - Standard haematology and biochemistry - Gallbladder ultrasound - Pituitary tumour size - ECG - Putative anti-lanreotide Autogel antibodies, anti-pegvisomant antibodies. Lanreotide and pegvisomant serum levels (minimum observed concentrations Cmin).
Additional Objectives: To assess the effect of lanreotide - pegvisomant co-administration on: • GH, GH binding protein, acid labile subunit, and prolactin levels. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At the screening visit: • Provision of written informed consent prior to any study related procedures. • Male or female aged between 18 and 75 years inclusive. • The patient must have had documentation supporting the diagnosis of acromegaly, including elevated GH and/or IGF-1 levels. • The patient is treated with pegvisomant, because of IGF-1 level remaining above ULN when treated with somatostatin analogue, on a daily basis for at least 3 months and has normal (age and sex adjusted) IGF-1 levels, or IGF-1 level above ULN after treatment with pegvisomant 30 mg per day, OR the patient is treated with lanreotide Autogel or octreotide LAR for at least 6 months including the last 3 months at the highest marketed dose, and has a serum IGF-1 level above ULN, 28 days after the last injection. At the end of the run-in period: • The patient has a serum IGF-1 level above 1.2 x ULN, or a serum IGF-1 level between ULN and a 1.2 x ULN and a serum GH nadir > 1 µg/L ( assessed by an OGTT), 28 days after the 3rd injection of lanreotide Autogel 120 mg. • The patient is diabetic and has a serum IGF-1 level above 1.2 x ULN, 28 days after the 3rd injection of lanreotide Autogel 120 mg. |
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E.4 | Principal exclusion criteria |
• The patient has undergone pituitary surgery or raditherapy within 6 months prior to study entry. • It is anticipated that the patient will receive pituitary surgery or radiotherapy during the study. • The patient has a history of hypersensitivity to lanreotide or pegvisomant or drugs with a similar chemical structure. • The patient has already been treated with a somatostatin analogue associated with a GH antagonist. • The patient has received a dopamine agonist within 6 weeks prior to study entry. • The patient has been treated with any unlicensed drug within the last 30 days before study entry. • The patient is likely to require treatment during the study with drugs that are not permitted by the study protocol. • The patient has abnormal hepatic function at study entry (defined as AST, ALT, GGT, alkaline phosphatase, prothrombin time or total bilirubin above 2 ULN). • The patient is at risk of pregnancy or is lactating. Females of childbearing potential must provide a negative pregnancy test within 5 days before the start of the study and must be using oral, double barrier or injectable contraception. Non childbearing potential is defined as post-menopause for at least one year, surgical sterilisation or hysterectomy at least three months before the start of the study. • The patient has a history of, or known current, problems with alcohol or drug abuse. • The patient has any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude. • The patient has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject’s safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the percentage of patients with normalised (age and sex adjusted) IGF-1 level at the end of the co-treatment period. |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the trial is defined as the last visit of the last patient 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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |