Evaluation of drug-drug interaction between LCZ696 and sildenafil in subjects with mild to moderate hypertension

• Register: EUCTR
• Last refreshed on: 4 November 2013
• Main ID: EUCTR2012-001632-64-DE
• Date of registration: 11/07/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Evaluation of drug-drug interaction between LCZ696 and sildenafil in subjects with mild to moderate hypertension
• Scientific title: An open label, three-period, single sequence study to evaluate the pharmacokinetic drug-drug interaction between LCZ696 and sildenafil in subjects with mild to moderate hypertension
• Date of first enrolment: 08/08/2012
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001632-64
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: open label, three-period, single sequence study If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Germany

Contacts

• Name: Medical Competence Center
• Affiliation: Novartis Pharma GmbH

• Name: Medical Competence Center
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

mild to moderate hypertension
MedDRA version: 14.1 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 - Vascular disorders

Intervention(s)

Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not assigned
CAS Number: 936623-90-4
Current Sponsor code: LCZ696
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Trade Name: Viagra
Product Name: Viagra
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sildenafil
CAS Number: 171599-83-0
Other descriptive name: sildenafil citrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: - 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

Secondary Objective: - To investigate the safety and tolerability of LCZ696, sildenafil, and their combination in subjects with mild to moderate hypertension

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)

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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From day -28 (screening) until 30 days past the final study assessment

Secondary end point(s): Number of patients with adverse events, serious adverse events and death

Secondary ID(s)

CLCZ696B2225

Source(s) of Monetary Support

Novartis Pharma Services AG