E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Caucasian males aged between 18 and 50 years of age (inclusive) with cystic fibrosis and pancreatic insufficiency able to discontinue their standard pancreatic enzyme therapy during the treatment phase of the study. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
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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 evaluate the safety, tolerability, and pharmacodynamics of multiple doses of LU 70274. To investigate the concentration of fat and lipase in stool. To investigate the intensity of abdominal pain and gastrointestinal discomfort.
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Able to understand and follow instructions during the study. 2. Signed informed consent. 3. Caucasian male patients aged between 18 and 50 years with CF transmembrane conductance regulator mutations on both alleles or two positive sweat tests, with pancreas insufficiency who are able to discontinue their standard pancreatic enzyme therapy during the treatment phase of the study (i.e., Study Days 2-4). 4. Pancreatic elastase E1 < 200 g/g in stool at screening, 5. General good physical health as determined by medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory tests. 6. Weight within the normal range according to accepted values for the Body mass index (BMI) within 18.5-29.9 kg/m2. 7. Normal blood pressure (Systolic Blood Pressure (SBP) >95, <139 mmHg; Diastolic Blood Pressure (DBP) >55, <90 mmHg) measured after 5 min rest in supine position. 8. A heart rate at rest of >45 and <99 b/min measured after 5 min rest in supine position. 9. ECG recording without clinically significant abnormalities. 10. Having had no febrile or infectious illness for at least seven days prior to the first administration of the IMPs of the study.
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E.4 | Principal exclusion criteria |
1. Acute exacerbations of CF. 2. History of infection with burkholderia cepacia (B. cepacia) or methicillin-resistant staphylococcus aureus within the last six months. 3. Clinically not acceptable lung function, as determined by FEV1 (Forced Expiratory Volume in one second) < 40% predicted 4. Distal Intestinal Obstruction Syndrome within the past 12 months. 5. Oral antacid therapy with H2-antagonists or proton pump inhibitors within the past 3 months. 6. Systemic corticosteroids within the past 3 months. 7. Positive test for human immunodeficiency virus (HIV) antibodies. 8. Positive hepatitis-B-virus-surface antigen (HBsAg) test. 9. Positive Anti-hepatitis-C-virus antibodies (Anti-HCV) test. 10. Laboratory values suggesting an unknown disease in the opinion of the investigator and/or requiring further clinical evaluation assessed by the investigator (especially ALT, aspartate aminotransferase (AST), gamma glutamyltranspeptidase (GGT)). 11. Any history of alcohol or drug abuse. 12. More than moderate alcohol consumption (>35 g of ethanol regularly per day or >245 g regularly per week). 13. Ethanol consumption within 48 hours prior to administration verified by alcohol breath test (Alcotest®). 14. Any history or suspicion of barbiturate, amphetamine, benzodiazepine, cocaine, opiates and cannabis abuse (verified by Mahsan "Kombi/DOA2-" and Mahsan "Kombi4/O2T Schnelltest"). 15. More than moderate smoker (>10 cigarettes/day). 16. Demonstrating excess in xanthine consumption (more than five cups of coffee or equivalent per day). 17. Any history of drug hypersensitivity that is assessed to be of clinical relevance, asthma, urticaria or other severe allergic diathesis. 18. Any history of hypersensitivity to the IMP. 19. Any disease state – other than CF – that, in the opinion of the investigator, does not allow study participation. 20. Participation in the treatment phase of a clinical study within 30 days prior to the treatment phase of this study. 21. Blood donation within 30 days prior to inclusion in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability: Physical examination, vital signs, electrocardiogram (ECG), adverse events (AEs), subjective well-being, clinical chemistry, hematology, urine analysis, and overall tolerability, total immunoglobulin G (IgG) in serum.
Pharmacodynamics: Fat in stool and stool weight.
Lipase concentrations in stool: Amount of lipase excreted. |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | No |
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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Last subject last visit (see chapter 9.3.3 and 9.3.4 of the protocol)
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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 | |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |