Clinical trial NCT01601470: Evaluation of Drug-drug Interaction Between LCZ696 and Sildenafil in Subjects With Mild to Moderate Hypertension
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild to Moderate Hypertension
Keywords: LCZ696, sildenafil, pharmacokinetics, mild to moderate hypertension
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-05-18
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: This study was conducted to investigate the potential for a pharmacokinetic drug-drug interaction in support of the co-administration of LCZ696 and sildenafil.

Detailed description: This study was conducted to investigate the potential for a pharmacokinetic drug-drug interaction in patients with mild-to-moderate hypertension in support of the co-administration of LCZ696 and sildenafil.

Eligibility criteria: Inclusion Criteria:

* Male subjects with mild to moderate hypertension, either treated or not currently on 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.
* 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;

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

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of LCZ696 Analytes
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of LCZ696 Analytes (AHU377, LBQ657 and Valsartan)
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Minimum Plasma Concentration Following Drug Administration at Steady State (Cmin,ss) of LCZ696 Analytes (AHU377, LBQ696 and Valsartan)
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax) of LCZ696 Analytes (AHU377, LBQ657 and Valsartan)
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sildenafil and N-desmethyl-sildenafil Analytes
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sildenafil and N-desmethyl-sildenafil Analytes
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Terminal Elimination Half-life (T1/2) of Sildenafil and N-desmethyl-sildenafil Analytes
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Maximum Plasma Concentration Following Drug Administration (Cmax) of Sildenafil and N-desmethyl-sildenafil Analytes
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax) of Sildenafil and N-desmethyl-sildenafil Analytes
timeFrame: From pre-dose on day 1 until 12 hours post dose on day 8
Secondary outcomes:
measure: Adverse Events, Serious Adverse Events and Deaths Were Monitored From Screening to End of Study
timeFrame: From the screening visit until 30 days past the final study assessment
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hsiao HL, Langenickel TH, Petruck J, Kode K, Ayalasomayajula S, Schuehly U, Greeley M, Pal P, Zhou W, Prescott MF, Sunkara G, Rajman I. Evaluation of Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild-to-Moderate Hypertension. Clin Pharmacol Ther. 2018 Mar;103(3):468-476. doi: 10.1002/cpt.759. Epub 2017 Nov 3.