3 Month PHI PAD PoM Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02135848
First received: June 28, 2012
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

This is a multi-center, randomized, blinded, placebo controlled study to evaluate the safety of GSK1278863 and its acute and short-term (e.g. 14d) effects on calf muscle endurance and walking ability in subjects with PAD and symptomatic claudication.


Condition Intervention Phase
Vascular Disease, Peripheral
Drug: GSK1278863
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Multi-center, Placebo-controlled Study to Evaluate the Safety and Efficacy of GSK1278863 vs. Placebo in Subjects With Peripheral Artery Disease (PAD).

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Spontaneous AE reporting [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Summary of ECGs [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Summary of vital signs [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Summary of nursing/physician observation [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total number of contractions [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Total work performed [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Total exercise time to onset of claudication and claudication-limited maximal muscle performance during a Bilateral Heel Raise Test [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Maximal distance covered during a Six-Minute Walk Test [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Changes in EPO concentration, hemoglobin, hematocrit, hsCRP, and lipids (TC, TG, HDLc, LDLc) [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]
  • AUC of GSK1278863 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Cmax of GSK1278863 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Ctau of GSK1278863 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Relationship of PK parameters to the pharmacodynamic assessments performed in this study [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: October 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1278863
Study Drug
Drug: GSK1278863
GSK1278863
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

Detailed Description:

This is a multi-center, randomized, blinded, placebo controlled study to evaluate the safety of GSK1278863 and its acute and short-term (e.g. 14d) effects on calf muscle endurance and walking ability in subjects with PAD and symptomatic claudication. Functional assessments will be performed following a single high dose (300mg), a single low dose (15mg), and following 14 days of low dose treatment (15mg q.d.). The objectives of this study are to: 1) Evaluate the safety and tolerability of GSK1278863 administered as a single dose and as sub-chronic low dosing (i.e. 14 days) in subjects with peripheral artery disease; 2) To demonstrate the potential pharmacodynamic effect of GSK1278863 on functional measures of calf muscle endurance and fatigability and timed walking distance following a single high or low dose and after 14 days of multiple low dose administration in subjects with claudication-limited peripheral artery disease. In this hypothesis-generating study, multiple assessments of ambulatory and skeletal muscle function will be made during standardized tests of claudication-limited exercise performance, and 3). Characterize the relationship, if any, between the doses and plasma concentrations of GSK1278863 and the pharmacodynamic effects.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects ≥ 40 years of age.
  • Male subjects must use one of the contraceptive methods listed in Section 8.1 for 90 days post-last dose.
  • Females must be postmenopausal, surgically sterilized, or practicing a suitable method of birth control so that in the opinion of the investigator they will not become pregnant during the course of the study.

A female subject is eligible to participate if she is of child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 30 days post-last dose.

  • Peripheral artery disease defined as an ankle-brachial index (ABI) at rest ≤ 0.90 in at least one leg in which the patient experiences claudication. For all subsequent evaluations, the Index Leg refers to the symptomatic leg with the lowest ABI.
  • Claudication symptoms with stable severity for at least 3 months prior to screening.
  • The patient is able to provide written informed consent to participate in this study.
  • AST and ALT < 2xULN; alkaline phosphatase and bilirubin greater than or equal too 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Confirmed QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with bundle branch block.
  • Subjects must be able to perform performance/exercise testing

Exclusion Criteria:

  • Coronary artery bypass graft (CABG), open peripheral vascular procedures, or major surgical procedures within 6 months prior to screening or patients likely to require revascularization during the course of the trial. Endovascular procedures within 3 months prior to screening.
  • Any unstable vascular syndromes (such as TIA, CVA, unstable angina or acute MI), including major changes to related medications, within 6 months prior to randomization.
  • Critical leg ischemia classified as Fontaine Stage III-IV (rest pain, tissue necrosis or gangrene).
  • Pregnant or nursing women (women capable of childbearing must have a negative pregnancy test).
  • A hemoglobin value at screening is:

Male subjects or post-menopausal females: > 15.5 g/dL Female subjects: > 14.5 g/dL

  • Active malignancy or diagnosis of malignancy within 5 years prior to screening (excluding successfully treated basal or squamous cell carcinoma).
  • Other clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, hematological, or metabolic disease that is, in the opinion of the Investigator or the Medical Monitor, not stabilized or may otherwise confound the results of the study.
  • Patients with a baseline medical history of proliferative diabetic retinopathy, preproliferative diabetic retinopathy, or wet age-related macular degeneration (AMD)
  • Previously enrolled in a gene therapy clinical study unless patient was randomized to placebo.
  • Plans to initiate a formal exercise training program during the course of the study, or initiation of a formal exercise training program within 3 months prior to screening.
  • Poorly controlled hypertension (defined as seated resting BP >160 mmHg systolic or > 95 mmHg diastolic, or both).
  • Hypotension (defined as seated resting BP < 95 mmHg systolic or < 55 mmHg diastolic, or both, or symptomatic hypotension [seated, supine, or orthostatic]).
  • Exercise tolerance, including bilateral heel raise and Six-Minute Walk Test performance, that is limited by co-morbid conditions or diseases other than claudication.
  • Poorly controlled diabetes defined as Hemoglobin A1c (HbA1c) > 10%.
  • Creatinine > 2.5 mg/dL or undergoing hemodialysis.
  • Thrombocytopenia defined as platelet count < 100,000/mm3 at screening.
  • Hematocrit ≤ 30% or ≥ 55%.
  • International Normalized Ratio (INR) > 1.5.
  • A positive Hepatitis B surface antigen or positive Hepatitis C antibody result if performed within 3 months of screening (testing not required at Screening).
  • History of alcohol or drug abuse, or a significant medical or psychiatric disorder that may impair compliance with the requirements of the protocol.
  • The patient has received an investigational drug within 30 days prior to this study.
  • The patient is enrolled or plans to enroll in another clinical trial during this study
  • History of venous thrombosis, defined as deep vein thrombosis, pulmonary embolism or other venous thrombotic condition, within 1 year prior to Screening.
  • Acute peptic ulcer disease or history of chronic rectal bleeding.
  • Patients with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Examples of conditions that could interfere with normal gastrointestinal anatomy or motility include gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue.
  • Use of prescription drugs within 7 days prior to first dose of study drug (Day 1) until after completion of all study drug doses and Day 35 assessments:

which are known to be inhibitors of CYP 2C8 OR which are known to be both CYP 2C8 and OATP1B1 substrates OR which rely mainly on OATP1B1/1B3 for hepatic clearance as described in Section 9 of the protocol.

  • Use of prescription drugs within 14 days prior to first dose of study drug (Day 1) until completion of all study drug doses and Day 35 assessments, which are known to be inducers of CYP 2C8, as described in Section 9 of the protocol.
  • Use of non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study drug (Day 1) through the Follow-up Visit (Day 65), unless, in the opinion of the Investigator, medication will not interfere with the study procedures or compromise subject safety and GSK Medical Monitor concurs.
  • History of sensitivity to any of the study drugs, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Patient is mentally or legally incapacitated.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02135848

Locations
United States, California
GSK Investigational Site
Palo Alto, California, United States, 94304
GSK Investigational Site
Vista, California, United States, 92083
United States, Florida
GSK Investigational Site
Clearwater, Florida, United States, 33761
GSK Investigational Site
Sarasota, Florida, United States, 34239
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60612
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46290
United States, North Carolina
GSK Investigational Site
Boone, North Carolina, United States, 28607
GSK Investigational Site
Durham, North Carolina, United States, 27705
United States, Ohio
GSK Investigational Site
Toledo, Ohio, United States, 43606
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78229
United States, Virginia
GSK Investigational Site
Norfolk, Virginia, United States, 23502
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02135848     History of Changes
Other Study ID Numbers: 114272
Study First Received: June 28, 2012
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases

ClinicalTrials.gov processed this record on August 27, 2014