Study to Investigate the Effect of GSK1014802 on Ambulatory Blood Pressure

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00955396
First received: August 6, 2009
Last updated: January 7, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Healthy Volunteer
Drug: GSK1014802
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: A Randomized, Double-blind, Placebo-controlled Cross-over Study to Investigate the Effect of GSK1014802 on Ambulatory Blood Pressure

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change in 24 h average SBP and DBP from Baseline to Day 36. [ Time Frame: 36 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 36 days ] [ Designated as safety issue: Yes ]
  • Change in day-time outpatient (6:00 AM to 10:00 PM) SBP and DBP from Baseline to Days 15 and 36. [ Time Frame: 36 days ] [ Designated as safety issue: Yes ]
  • Change in night-time outpatient (10:00 PM to 6:00 AM) SBP and DBP from Baseline to Days 15 and 36. [ Time Frame: 36 days ] [ Designated as safety issue: Yes ]
  • Change in 24 h average ambulatory heart rate from Baseline to Days 15 and 36. [ Time Frame: 36 days ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 36 days ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • PK parameters of GSK1014802 following repeated oral doses of GSK1014802 given twice daily to healthy male and female subjects: Cmax, tmax, AUC(0-12). [ Time Frame: 36 days ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 36 days ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: July 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Period 1 Drug: GSK1014802
Tablets
Drug: Placebo
Tablets
Period 2 Drug: GSK1014802
Tablets
Drug: Placebo
Tablets

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00955396

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14202
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00955396     History of Changes
Other Study ID Numbers: 113210
Study First Received: August 6, 2009
Last Updated: January 7, 2010
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by GlaxoSmithKline:
sodium channel blocker
ambulatory blood pressure

Additional relevant MeSH terms:
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014