Study to Investigate the Effect of GSK1014802 on Ambulatory Blood Pressure

A Randomized, Double-blind, Placebo-controlled Cross-over Study to Investigate the Effect of GSK1014802 on Ambulatory Blood Pressure

In this study the investigators will determine whether there is any effect of GSK1014802 on ambulatory blood pressure. This will be a randomized, double-blind, placebo-controlled, repeat dose, 2 period cross-over study conducted in healthy male and female subjects. Approximately 60 subjects will be randomised to receive GSK1014802 400 mg bid and placebo for 36 days with at least 1 week between treatment sessions. A follow-up will occur 7-14 days after the last dose.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Placebo; Drug: GSK1014802

Detailed Description

This study, previously posted by GlaxoSmithKline (GSK), was transitioned to Convergence Pharmaceuticals, Ltd., which spun off from GSK. Convergence Pharmaceuticals, Ltd., has now been acquired by Biogen.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14202
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between 18 and 65 years of age inclusive.
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, liver function and cardiac monitoring.
• A female subject is eligible to participate if she is of:

Non-childbearing potential Child-bearing potential and agrees to use a contraception method.

• Male subjects must agree to use a contraception methods
• Body weight ≥ 50 kg and BMI within the range 19 - 40.0 kg/m2 (inclusive).
• Arm circumference ≥ 24 and ≤ 42 cm at mid level.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug screen.
• Alcohol levels above the legal limit for driving at screening and the detection of any alcohol within 24 h prior to the start of dosing in Treatment Periods 1 and 2.
• A positive test for HIV antibody.
• History of regular excessive alcohol consumption within 6 months of the study
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Use of prescription or non-prescription drugs, including any antihypertensive agent including diuretics, vitamins, herbal and dietary supplements
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• Subjects who work at night or whose work schedule includes rotating night time (10:00 PM to 6:00 AM) work.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Average daily caffeine intake equivalent to > 4 cups of coffee or > 6 cups of tea.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
• Consumption of aged cheeses and meats, soy sauce and other tyramine rich sources within 1 day prior to the baseline assessments.
• Current or past history of symptomatic orthostatic hypotension or history of unexplained vasovagal episode(s).
• History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).
• Any history of suicidal behaviour or suicidal ideation of type 4 or 5 on the C-SSRS within 3 months of the screening visit.
• History or currently diagnosed sleep apnea.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Period 1	Drug: Placebo; Tablets; Drug: GSK1014802; Tablets; Other Names: BIIB074 and CNV1014802
Other: Period 2	Drug: Placebo; Tablets; Drug: GSK1014802; Tablets; Other Names: BIIB074 and CNV1014802

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in 24 h average SBP and DBP from Baseline to Day 36.	36 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in 24 h average SBP and DBP from Baseline to Day 15. Change in average SBP and DBP within a dosing interval (12 h) from Baseline to Days 14 and 35.	35 days
Change in 24 h average SBP and DBP from Baseline to Days 15 and 36 in subjects with baseline SBP 120-139 mmHg and also DBP 80-89 mmHg.	36 days
Change in day-time outpatient (6:00 AM to 10:00 PM) SBP and DBP from Baseline to Days 15 and 36.	36 days
Change in night-time outpatient (10:00 PM to 6:00 AM) SBP and DBP from Baseline to Days 15 and 36.	36 days
Change in 24 h average ambulatory heart rate from Baseline to Days 15 and 36.	36 days
Proportion of patients whose 24 h systolic and diastolic BP increased by < 5, 5-9, 1014, 15-19, and > 20 mm Hg compared to baseline.	36 days
PK parameters of GSK1014802 following a single oral dose of GSK1014802 to healthy female subjects: Cmax, tmax, AUC (0-t) and, if possible, AUC(0-∞), λz and terminal phase half-life to healthy female subjects.	1 day
PK parameters of GSK1014802 following repeated oral doses of GSK1014802 given twice daily to healthy male and female subjects: Cmax, tmax, AUC(0-12).	36 days
PK/PD analyses to examine the correlation between ambulatory blood pressure and plasma levels and/or metrics of the systemic exposure (Cmax, AUC) of GSK1014802.	36 days

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Biogen Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2009
• Primary Completion (Actual): December 31, 2009
• Study Completion (Actual): December 31, 2009

Study Registration Dates

• First Submitted: August 6, 2009
• First Submitted That Met QC Criteria: August 6, 2009
• First Posted (Estimate): August 10, 2009

Study Record Updates

• Last Update Posted (Actual): October 16, 2017
• Last Update Submitted That Met QC Criteria: October 13, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: ambulatory blood pressure; sodium channel blocker
• Other Study ID Numbers: 113210; SCB113210