EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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).
Trial 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.
Primary purpose:
Basic Science
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Number of participants with adverse events (AE) and serious adverse events (SAE)
Timeframe: Up to 67 days
Number of participants with abnormal electrocardiogram (ECG) findings
Timeframe: Up to 39 days
Number of participants with vital signs of potential clinical importance
Timeframe: Up to 39 days
Number of participants with clinical chemistry abnormalities of potential clinical importance
Timeframe: Up to 67 days
Number of participants with clinical hematology abnormalities of potential clinical importance
Timeframe: Up to 67 days
Secondary outcomes:
Change from Baseline in total number of contractions to onset of claudication
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in total work performed to onset of claudication
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in total exercise time to onset of claudication
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in total number of contractions to claudication-limited maximal muscle performance
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in total work performed to claudication-limited maximal muscle performance
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in total exercise time to claudication-limited maximal muscle performance
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in the maximal distance covered during a Six-Minute Walk Test
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in Erythropoietin concentration
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in Hemoglobin
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in hematocrit
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in High sensitivity C-reactive protein (hsCRP)
Timeframe: Baseline (Day 1) to Day 39
Change from Baseline in lipids (Total cholesterol [TC], Triglycerides [TG], High density lipoprotein cholesterol [HDLc] and Low density lipoprotein cholesterol [LDLc])
Timeframe: Baseline (Day 1) to Day 39
Derived Plasma GSK1278863 Pharmacokinetic Parameter- Maximum plasma concentration (Cmax) and trough concentration (Ctau)
Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)
Derived Plasma GSK1278863 Pharmacokinetic Parameter -Area under the curve (AUC [0-t])
Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)
Derived Plasma GSK1278863 Pharmacokinetic Parameter - Time to maximum plasma concentration (T-max) and last time point where the concentration is above the limit of quantification (T-last)
Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)
Relationship of pharmacokinetic parameters to the pharmacodynamic assessments performed in this study
Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)
Interventions:
Drug: GSK1278863
Drug: Placebo
Enrollment:
46
Observational study model:
Not applicable
Primary completion date:
2011-01-11
Time perspective:
Not applicable
Clinical publications:
Eric Olson, PhD, Laura Demopoulos, MD, Thomas Haws, Erding Hu, PhD, Zixing Fang, PhD, Kelly Mahar, PhD, Pu Qin, PhD, John Lepore, MD, Tim Baur, PhD, Bill Hiatt, MD.Short-Term administration of a prolyl hydroxylase inhibitor failed to improve measures of performance in subjects with claudication-limited peripheral artery disease.Vasc Med.2014;19:473-482
Medical condition
Vascular Disease, Peripheral
Product
daprodustat
Collaborators
Not applicable
Study date(s)
October 2010 to November 2011
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
40+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Boone, North Carolina, United States, 28607
Status
Study Complete
Location
GSK Investigational Site
Chicago, Illinois, United States, 60612
Status
Study Complete
Location
GSK Investigational Site
Clearwater, Florida, United States, 33761
Status
Study Complete
Location
GSK Investigational Site
Durham, North Carolina, United States, 27705
Status
Study Complete
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46290
Status
Study Complete
Location
GSK Investigational Site
Norfolk, Virginia, United States, 23502
Status
Study Complete
Location
GSK Investigational Site
Palo Alto, California, United States, 94304
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Study Complete
Location
GSK Investigational Site
Sarasota, Florida, United States, 34239
Status
Study Complete
Location
GSK Investigational Site
Vista, California, United States, 92083
Status
Study Complete
Study documents
Study report synopsis
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2011-01-11
Actual study completion date
2011-01-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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