E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild and moderate hepatic impairment |
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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] - Digestive System Diseases [C06] |
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 | 10024670 |
E.1.2 | Term | Liver disorder |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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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 |
This is a study to characterize the pharmacokinetics as well as safety and tolerability of a single oral dose of LCZ696 200 mg in subjects with mild and moderate hepatic impairment compared to matched healthy subjects. |
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability of LCZ696 200 mg administered as single dose in subjects with mild and moderate hepatic impairment and their matched healthy control subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- All subjects:
• Male and female subjects aged 18-75 years.
• Body weight at least 55 kg with a body mass index between 18-35 kg/m2.
- Hepatic impairment subjects:
• Mild or moderate hepatic impairment. |
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E.4 | Principal exclusion criteria |
- All subjects:
• Clinical manifestations of postural symptomatic hypotension at screening or baseline.
• History of hypersensitivity to LCZ696 or to drugs of similar classes.
- Hepatic impairment subjects:
• Hepatic impairment due to non-liver disease.
• Treatment with any vasodilator, autonomic alpha blocker or beta2 agonist within 2 weeks of dosing.
• Encephalopathyy Stage III or IV.
• Primary biliary liver cirrhosis or biliary obstruction.
• History of gastro-intestinal bleeding within 3 months prior to screening.
- Healthy subjects:
• Any surgical or medical condition which might significantly alter the distribution, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
• Use of prescription drugs, herbal supplements, and/or over-the-counter medication, dietary supplements (vitamins included) within 2 weeks prior to initial dosing. Other protocol-defined inclusion/exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCZ696 analytes (AHU377, LBQ657, and valsartan).
- Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCZ696 analytes (AHU377, LBQ657, and valsartan).
- Maximum plasma concentration (Cmax) for LCZ696 analytes (AHU377, LBQ657, and valsartan). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From pre-dose on Day 1 until 96h post-dose (Day 5). |
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E.5.2 | Secondary end point(s) |
Number of participants with adverse events, serious adverse events and death. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From the screening visit until Day 5. |
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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 | No |
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 | Yes |
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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 |
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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
| 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 | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |