To Evaluate Pharmacokinetics of LFF269 in Healthy Volunteers and Patients With Hypertension

A Two Part Study Including a Randomized, Double Blind, Placebo Controlled, Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LFF269 After b.i.d Dosing in Healthy Volunteers and an Open Label, Multiple Dose Pharmacokinetics Study in Hypertension Subjects

This study is designed to enable optimal dose selection of LFF269 for potential future studies by providing additional information about the compounds safety, tolerability, pharmacokinetic and pharmacodynamic profiles.

Study Overview

• Status: Terminated
• Conditions: Part 1 - Healthy Volunteers; Part 2 - Patients With Hypertension
• Intervention / Treatment: Drug: Placebo to LFF269; Drug: LFF269

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Part 1

- Healthy men and women of non-childbearing potential, 18 to 80 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.

Part 2

• Hypertensive men and women of non-childbearing potential, 18 to 80 years of age inclusive.
• Patients with mild-to-moderate uncomplicated essential hypertension

Exclusion Criteria:

Part 1

• History of hypersensitivity or allergy to any of the study drugs or to drugs of similar chemical classes.
• A history of clinically significant ECG abnormalities.
• Known history or current clinically significant arrhythmias.
• History of hypertension, adrenal or endocrine disease.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
• Smokers (use of tobacco products in the previous 3 months).
• History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
• A positive Hepatitis B surface antigen or Hepatitis C test result.

Part 2

• Pregnant or nursing (lactating) women.
• Women of child-bearing potential.
• Known history or evidence of a secondary form of hypertension
• Type 1 or type 2 diabetes mellitus.
• History of heart diseases
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
• History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.

Other protocol defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo to LFF269 (Part 1); Placebo to LFF269 twice daily (b.i.d) for 10 days in healthy volunteers	Drug: Placebo to LFF269; Placebo LFF269 b.i.d for 10 days in healthy volunteers; Other Names: placebo
Experimental: LFF269 (Part 1); LFF269 twice daily (b.i.d) for 10 days in healthy volunteers	Drug: LFF269; LFF269 capsules twice daily (b.i.d); Other Names: LFF269 active
Experimental: LFF269 (Part 2); LFF269 twice daily (b.i.d) for 5 days in patients with hypertension	Drug: LFF269; LFF269 capsules twice daily (b.i.d); Other Names: LFF269 active

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of healthy volunteers reported with adverse events as an assessment of safety and tolerability (Part 1)	10 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)[Part 1- Healthy volunteers]	Day 1
Observed maximum plasma concentration following drug administration (Cmax) at day 1 [Part 1- Healthy volunteers]	Day 1
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) [Part 2- Patients with hypertension]	Day 1
Observed maximum plasma concentration following drug administration (Cmax) at day 1 [Part 2 - Patients with hypertension]	Day 1
Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state (AUCtau,ss) [Part 1- Healthy volunteers]	Day 10
Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state (AUCtau,ss) [Part 2 - Patients with hypertension]	Day 5
Observed maximum plasma concentration following drug administration at steady state (Cmax,ss) [Part 2 - Patients with hypertension]	Up to Day 5
Observed maximum plasma concentration following drug administration at steady state (Cmax,ss) [Part 1- Healthy volunteers]	Up to Day 10
Number of patients reported with adverse events as an assessment of safety and tolerability (Part - 2, Patient with Hypertension)	5 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: January 26, 2014
• First Submitted That Met QC Criteria: January 26, 2014
• First Posted (Estimate): January 28, 2014

Study Record Updates

• Last Update Posted (Estimate): April 1, 2016
• Last Update Submitted That Met QC Criteria: March 30, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Healthy volunteers, hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CLFF269X2105