E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
mild to moderate hypertension |
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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] - Cardiovascular Diseases [C14] |
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 | 10020772 |
E.1.2 | Term | Hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular 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 |
- To investigate the effect of LCZ696 on single dose pharmacokinetics of sildenafil in subjects with mild to moderate hypertension.
- To investigate the effect of sildenafil on the steady-state pharmacokinetics of the LCZ696 analytes in subjects with mild to moderate hypertension |
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E.2.2 | Secondary objectives of the trial |
- To investigate the safety and tolerability of LCZ696, sildenafil, and their combination in subjects with mild to moderate hypertension |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male subjects with mild to moderate hypertension, either treated or not surrently under treatment, between age 18 and 65 years of age, and otherwise in good health as determined by past medical history , physical examination, vital signs, electrocardiogram, and laboratory tests at screening except for hypertension
- At screening: systolic blood pressure 120-140 mmHg on therapy, or 140-160 mmHg if untreated
- At screening: diastolic blood pressure, 70-95 mmHg on therapy, or 90-100 mmHg if untreated
- Baseline:BP >= 140/90
- Subjects currently on hypertension treatment should be on stable single drug antihypertensive medication during 2 months prior to screening
For detailed inclusion criteria see the full protocol. |
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E.4 | Principal exclusion criteria |
- Use of non-antihypertensive prescription drugs, herbal supplements, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing
- History of documented symptomatic orthostatic hypotension or syncope
For detailed exclusion criteria see the full protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Pharmacokinetics of LCZ696: Area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau)
-Pharmacokinetics of LCZ696: Observed maximum plasma concentration following drug administration at steady state (Cmax, ss)
- Pharmacokinetics of LCZ696: Observed minimum plasma concentration following drug administration at steady state (Cmin, ss)
- Pharmacokinetics of LCZ696: Time to reach the maximum concentration after drug administration (Tmax)
- Pharmacokinetics of Sildenafil and N-desmethyl sildenafil: Area under the plasma concetration-time curve from time zero to infinity (AUCinf)
- Pharmacokinetics of Sildenafil and N-desmethyl sildenafil: Area under the plasma concetration-time curve from time zero to the time of the last quantifiable concentration
- Pharmacokinetics of Sildenafil and N-desmethyl sildenafil:Terminal elimination half-life (T1/2)
- Pharmacokinetics of Sildenafil and N-desmethyl sildenafil:Observed maximum plasma concentration following drug administration (Cmax)
- Pharmacokinetics of Sildenafil and N-desmethyl sildenafil:Time to reach the maximum concentration after drug administration (Tmax) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose
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E.5.2 | Secondary end point(s) |
Number of patients 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 day -28 (screening) until 30 days past the final study assessment |
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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 | 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 | 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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
open label, three-period, single sequence study |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |