Study to Investigate the Effect of GSK1014802 on Ambulatory Blood Pressure
This study has been completed.
Sponsor:
GlaxoSmithKline
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00955396
First received: August 6, 2009
Last updated: January 7, 2010
Last verified: January 2010
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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
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 May 23, 2013