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 | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007270 |
E.1.2 | Term | Carcinoid syndrome |
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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 repeated s.c. injections at different doses of BIM 23A760 on patient’s overall satisfaction in terms of symptom relief (diarrhoea and/or flushes) in patients with carcinoid syndrome after 24 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
•To assess the efficacy of repeated s.c. injections at different doses of BIM 23A760 on carcinoid symptoms (diarrhoea and/or flushes) • To assess the efficacy of BIM 23A760 on quality of life (QoL) • To assess the efficacy of BIM 23A760 on 5-HIAA and chromogranin A • To investigate the safety and tolerability of BIM 23A760 administered by repeated s.c. injections at different doses to patients with carcinoid syndrome • To investigate the PK of BIM 23A760 administered by repeated s.c. injections at different doses to patients with carcinoid syndrome. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient has provided written informed consent prior to any study related procedures. 2. Male or female, between 18 and 75 years inclusive. 3. Females of childbearing potential must provide a negative pregnancy test at the start of the study. Female patients who are at risk of becoming pregnant must agree to use an effective method of contraception such as double barrier contraception, an injectable or implanted hormonal contraceptive, combined oral contraceptive or an intra-uterine device (IUD). The patient must agree to use the contraception for two months after the last investigational medicinal product (IMP) administration. Nonchildbearing potential is defined as being postmenopausal for at least 1 year, or permanently sterilised at least 3 months before study entry. 4. Male patients must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception (see above). 5. The patient has a carcinoid syndrome defined as ≥3 stools/day and/or ≥3 flushes/week at study entry (Visit 1). This will be confirmed at Visit 2 by reviewing the information provided in the patient diary card during the screening period. 6. The patient has a well-differentiated mid-gut carcinoid tumour or serotonin secreting tumour of unknown localisation with hepatic metastasis (documented biopsy). 7. The patient has elevated 5-HIAA (above the upper limit of normal (ULN)). |
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E.4 | Principal exclusion criteria |
1. The patient has undergone surgery related to a neuroendocrine tumour (NET) within 4 weeks prior to study entry or has surgery planned during the study. 2. The patient has received short acting somatostatin analogues (SSAs) within 2 weeks before study entry or has received short acting SSAs for more than 3 months. 3. The patient has received a radiolabelled SSA at any time before study entry. 4. The patient has received long acting SSAs as follows: • More than three injections at any time before study entry • Between one and three injections, with the last injection within the period before study entry referenced below.
Lanreotide Lanreotide Lanreotide Autogel 60mg Autogel 90mg Autogel 120mg or Octreotide or Octreotide or Octreotide LAR 10mg LAR 20mg LAR 30MG
1 injection 6 weeks 8 weeks 10 weeks 2 injections 8 weeks 10 weeks 12 weeks 3 injections 10 weeks 12 weeks 14 weeks
5. The patient has a pancreatic tumour or a bronchial tumour. 6. The patient has previously received any specific anti-tumour treatment such as chemotherapy, (chemo)embolisation, radiotherapy or interferon in the last 6 months or is anticipated to receive any of these treatments during the study (based on Investigator’s judgement). 7. The patient is lactating or at risk of lactating during the study. 8. The patient has signs or symptoms of cardiac insufficiency. 9. The patient has an ejection fraction <40% and/or clinically severe cardiac valvular regurgitation, centrally assessed during the screening period. 10. The patient has uncontrolled arterial hypertension. 11. The patient has had a previous cancer (except basocellular carcinoma of the skin and/or in situ carcinoma of the cervix/uterus). Patients with a history of cancer that was not basocellular carcinoma of the skin or in situ carcinoma of the cervix/uterus can be included if they have been treated with curative intent and have been free from disease for more than 5 years. 12. The patient has received BIM 23A760 prior to the study. 13. The patient has uncontrolled diabetes (glycosylated haemoglobin (HbA1c) > 8%). 14. The patient has insulin treated diabetes and has been treated for less than 6 months prior to study entry. 15. The patient has any clinically significant hepatic abnormalities and/or aspartate aminotransferase (AST) >3 x ULN and/or alanine aminotransaminase (ALT) >3 x ULN and/or alkaline phosphatase (ALP) >3 x ULN and/or conjugated bilirubin >1.5 x ULN during the screening period. 16. The patient has abnormal findings during the screening period, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient’s safety. 17. The patient has been treated with any other IMP prior to the first study visit without undergoing a washout period of seven times the elimination half-life of the IMP. 18. The patient has a known hypersensitivity to any of the test materials or related compounds. 19. The patient is likely to require treatment during the study with drugs that are not permitted by the study protocol. 20. The patient has a history of, or known current, problems with alcohol or drug abuse. 21. The patient has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an unco-operative attitude. 22. The patient belongs to any hierarchical, patient or other group where they may have been unduly influenced to participate in the trial (e.g. patients committed to an institution by virtue of an order issued either by any judicial or administrative authorities). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of patients with a positive overall satisfactory relief of symptoms on the Likert score after 24 weeks 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 | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 |
adaptive - The number of patient treated at a starting dose will depend on a data review commitee |
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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
| 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 | 40 |
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 | Information not present in EudraCT |
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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |