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Completed

NCT Number: NCT01601470

Evaluation of Drug-drug Interaction Between LCZ696 and Sildenafil in Subjects With Mild to Moderate Hypertension

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

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Key information

Conditions

Mild to Moderate Hypertension

Age range

18 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site

Berlin, 14050, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LCZ696

Drug

LCZ696 400mg QD was administered alone for 4 days and in combination with sildenafil for 1 day

Sildenafil

Drug

Sildenafil 50 mg single dose was administered alone for 1 days and in combination with LCZ696 400mg QD for 1 day

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of LCZ696 Analytes

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of sildenafil on the pharmacokinetics of LCZ696 (analytes of LCZ696: AHU377, LBQ657 and valsartan) was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, and day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. AUC is a mathematically-derived value from all measurements. AUC is a measure of the area under the curve that is obtained from plotting the plasma concentration by time point. All time-points were used to derive the single PK parameters.

  2. Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of LCZ696 Analytes (AHU377, LBQ657 and Valsartan)

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of sildenafil on the pharmacokinetics of LCZ696 (analytes of LCZ696: AHU377, LBQ657 and valsartan) was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, and day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. Cmax is a mathematically-derived value from all measurements. Cmax is a measure of the area under the curve that is obtained from plotting the plasma concentration by time point. All time-points were used to derive the single PK parameters.

  3. Minimum Plasma Concentration Following Drug Administration at Steady State (Cmin,ss) of LCZ696 Analytes (AHU377, LBQ696 and Valsartan)

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of sildenafil on the pharmacokinetics of LCZ696 (analytes of LCZ696: AHU377, LBQ657 and valsartan) was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. Cmin is a mathematically-derived value from all measurements. Cmin is a measure of the area under the curve that is obtained from plotting the plasma concentration by time point. All time-points were used to derive the single PK parameters.

  4. Time to Reach the Maximum Concentration After Drug Administration (Tmax) of LCZ696 Analytes (AHU377, LBQ657 and Valsartan)

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of sildenafil on the pharmacokinetics of LCZ696 (analytes of LCZ696: AHU377, LBQ657 and valsartan) was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. Tmax is a mathematically-derived value from all measurements. Tmax is a measure of the area under the curve that is obtained from plotting the plasma concentration by time point. All time-points were used to derive the single PK parameters.

  5. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sildenafil and N-desmethyl-sildenafil Analytes

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of LCZ696 on the pharmacokinetics of Sildenafil and N-desmethyl-sildenafil was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. AUC is a mathematically-derived value from all measurements. AUC is a measure of the area under the curve that is obtained from plotting the plasma concentration by time point. All time-points were used to derive the single PK parameters.

  6. 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

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of LCZ696 on the pharmacokinetics of Sildenafil and N-desmethyl-sildenafil was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. AUC is a mathematically-derived value from all measurements. AUC is a measure of the area under the curve that is obtained from plotting the plasma concentration by time point. All time-points were used to derive the single PK parameters.

  7. Terminal Elimination Half-life (T1/2) of Sildenafil and N-desmethyl-sildenafil Analytes

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of LCZ696 on the pharmacokinetics of Sildenafil and N-desmethyl-sildenafil was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. T1/2 is a mathematically-derived value from all measurements. T1/2 is a measure of the area under the curve that is obtained from plotting the plasma concentration by time point. All time-points were used to derive the single PK parameters.

  8. Maximum Plasma Concentration Following Drug Administration (Cmax) of Sildenafil and N-desmethyl-sildenafil Analytes

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of LCZ696 on the pharmacokinetics of Sildenafil and N-desmethyl-sildenafil was assessed. Blood samples were collected at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. All time-points were used to mathematically derive the single PK parameter.

  9. Time to Reach the Maximum Concentration After Drug Administration (Tmax) of Sildenafil and N-desmethyl-sildenafil Analytes

    Time frame: From pre-dose on day 1 until 12 hours post dose on day 8

    The effect of co-administration of LCZ696 on the pharmacokinetics of Sildenafil and N-desmethyl-sildenafil will be assessed. 8pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose from day 1 to day 7, 24 hours post-dose from day 7, day 8 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose. All time-points were used to mathematically derive the single PK parameter.

Secondary outcomes

  1. Adverse Events, Serious Adverse Events and Deaths Were Monitored From Screening to End of Study

    Time frame: From the screening visit until 30 days past the final study assessment

    Number of patients with adverse events, serious adverse events and death

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
May 18, 2012
Registry last updated
Oct 7, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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