Vascular Disease, PeripheralPhase 2NCT02135848

3 Month PHI PAD PoM Study

A Phase 2 study testing GSK1278863 in people with Vascular Disease, Peripheral, run by GlaxoSmithKline at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 years and older
Conditions the study is for: Vascular Disease, Peripheral
What is being tested?: GSK1278863
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 46 participants
Where: 12 sitesUnited States
Study dates: 15 Oct 2010to 1 Nov 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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

Who cannot join

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

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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 locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

United States12 sites

GSK Investigational Site
Boone, North Carolina, 28607
GSK Investigational Site
Chicago, Illinois, 60612
GSK Investigational Site
Clearwater, Florida, 33761
GSK Investigational Site
Durham, North Carolina, 27705
GSK Investigational Site
Indianapolis, Indiana, 46290
GSK Investigational Site
Norfolk, Virginia, 23502
GSK Investigational Site
Palo Alto, California, 94304
GSK Investigational Site
Philadelphia, Pennsylvania, 19104
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
Sarasota, Florida, 34239
GSK Investigational Site
Toledo, Ohio, 43606
GSK Investigational Site
Vista, California, 92083

Other trials in United States

About this study

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).

Read the 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.

Conditions: Vascular Disease, Peripheral
Being tested: GSK1278863, Placebo
Medical subject headings: Peripheral Vascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK1278863Drug
GSK1278863
PlaceboDrug
Placebo

Study groups in NCT02135848
Study group	Role	What they receive
GSK1278863	Experimental	Study Drug Receives: Drug: GSK1278863
Placebo	Placebo comparator	Placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Measured: Up to 67 days
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Twelve lead ECGs were recorded with the participant lying supine, having rested in this position for at least 5 minutes before each recording. Full 12 lead ECGs were recorded using an ECG device that automatically calculated the heart rate and measured PR, QRS, RR, QT and QT, QT corrected by Bazett's formula (QTcB) and QT corrected by Fridericia's formula (QTcF) intervals. Number of participants with abnormal (not clinically significant [NCS] and clinically significant [CS]) ECG findings are presented.
Measured: Up to 39 days
Number of Participants With Vital Signs of Potential Clinical Importance
Vital signs included heart rate, systolic and diastolic blood pressure and were performed with the participant in a supine position after the participant had rested for at least 5 minutes. Number of participants with vital signs of potential clinical importance are presented.
Measured: Up to 39 days
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
Clinical chemistry analyte of potential clinical concern included albumin, calcium, creatinine, glucose, magnesium, phosphorus, potassium, sodium and bicarbonate. Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.
Measured: Up to 67 days
Number of Participants With Clinical Hematology Abnormalities of Potential Clinical Importance
Hematology parameters included platelet count, red blood cell (RBC) count, white blood cell WBC count (absolute), hemoglobin, hematocrit, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils. Number of participants with clinical hematology abnormalities of potential clinical importance are presented.
Measured: Up to 67 days

Secondary outcomes (16)

Change From Baseline in Total Number of Contractions to Onset of Claudication
At Visit 1 (-21 to -10 days), the participant was introduced to the bilateral heel raise test (BHRT). Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg. Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. The index leg was defined as the leg that met the inclusion symptomatic and hemodynamic criteria (ankle brachial index [ABI] ≤ 0.90) with the lowest ABI considered if both legs were affected. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Total Work Performed to Onset of Claudication
BHRT is a method to assess muscle performance in participants with claudication. Participants with peripheral artery disease (PAD) and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to BHRT. Test familiarization consisted of the participant performing heel raises to onset of claudication. BHRT was conducted with an electrogoniometer instrumented on the index leg (leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until participant stopped due to intolerable claudication pain/fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Total Exercise Time to Onset of Claudication
BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance
BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance
BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance
BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test
The Six-Minute Walk Test was performed by the participant walking at a self-selected pace for 6 minutes through a pre-defined walking course. When the Six-Minute Walk Test and Bilateral Heel Raise Test were conducted at the same study visit, the participant was allowed to rest a minimum of one hour between these tests. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Erythropoietin Concentration
Blood samples for analysis of fasting levels of erythropoietin, was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Hemoglobin
Blood samples for analysis of fasting levels of hemoglobin was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in Hematocrit
Blood samples for analysis of fasting levels of hematocrit was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)
Blood samples for analysis of fasting levels of hsCRP, was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.
Measured: 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])
Blood samples for analysis of fasting levels of lipid panel (TC, TG, HDLc and LDLc) was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.
Measured: Baseline (Day 1) to Day 39
Derived Plasma GSK1278863 Pharmacokinetic Parameter- Maximum Plasma Concentration (Cmax) and Trough Concentration (Ctau)
Blood samples for pharmacokinetic analysis of GSK1278863 and selected metabolites were collected at the following time points: Visit 2-Baseline acute: pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3-post acute, Visit 4-rescreen, Visit 5-Baseline chronic and end of treatment or early termination. The actual date and time of each blood sample collection was recorded.
Measured: 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])
Blood samples for pharmacokinetic analysis of GSK1278863 and selected metabolites were collected at the following time points: Visit 2-Baseline acute: pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3-post acute, Visit 4-rescreen, Visit 5-Baseline chronic and end of treatment or early termination. The actual date and time of each blood sample collection was recorded.
Measured: 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)
Blood samples for pharmacokinetic analysis of GSK1278863 and selected metabolites were collected at the following time points: Visit 2-Baseline acute: pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3-post acute, Visit 4-rescreen, Visit 5-Baseline chronic and end of treatment or early termination. The actual date and time of each blood sample collection was recorded.
Measured: 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
A formal pharmacokinetic /pharmacodynamic analysis and pharmacokinetic /pharmacodynamic modelling for exposure relationships to endpoints was planned. The data for this outcome was not collected.
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Oct 20101 Nov 2011

First posted12 May 2014 (estimated)
Study start15 Oct 2010
Primary completion1 Nov 2011
Study completion1 Nov 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Vascular Disease, PeripheralStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02135848
Sponsor's protocol ID: 114272
Status last verified: Aug 2017
First submitted: 28 Jun 2012
Last updated: 20 Oct 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease
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All Vascular Disease, Peripheral trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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).
ClinicalTrials.gov ID: NCT02135848
Acronym / sponsor ID: 114272
Conditions: Vascular Disease, Peripheral
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 15 Oct 2010 (actual)
Primary completion: 1 Nov 2011 (actual)
Study completion: 1 Nov 2011 (actual)
First posted: 12 May 2014 (estimated)
Results: Posted 20 Oct 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
GSK1278863	Experimental	Drug: GSK1278863Study Drug
Placebo	Placebo comparator	Drug: PlaceboPlacebo

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (32 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK1278863GSK1278863	Drug	GSK1278863
PlaceboPlacebo	Drug	Placebo

Primary outcome

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time frame: Up to 67 days
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to 39 days
Twelve lead ECGs were recorded with the participant lying supine, having rested in this position for at least 5 minutes before each recording. Full 12 lead ECGs were recorded using an ECG device that automatically calculated the heart rate and measured PR, QRS, RR, QT and QT, QT corrected by Bazett's formula (QTcB) and QT corrected by Fridericia's formula (QTcF) intervals. Number of participants with abnormal (not clinically significant [NCS] and clinically significant [CS]) ECG findings are presented.
Number of Participants With Vital Signs of Potential Clinical Importance
Time frame: Up to 39 days
Vital signs included heart rate, systolic and diastolic blood pressure and were performed with the participant in a supine position after the participant had rested for at least 5 minutes. Number of participants with vital signs of potential clinical importance are presented.
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
Time frame: Up to 67 days
Clinical chemistry analyte of potential clinical concern included albumin, calcium, creatinine, glucose, magnesium, phosphorus, potassium, sodium and bicarbonate. Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.
Number of Participants With Clinical Hematology Abnormalities of Potential Clinical Importance
Time frame: Up to 67 days
Hematology parameters included platelet count, red blood cell (RBC) count, white blood cell WBC count (absolute), hemoglobin, hematocrit, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils. Number of participants with clinical hematology abnormalities of potential clinical importance are presented.

16 secondary outcomes

Change From Baseline in Total Number of Contractions to Onset of Claudication
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Total Work Performed to Onset of Claudication
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Total Exercise Time to Onset of Claudication
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Erythropoietin Concentration
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Hemoglobin
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in Hematocrit
Time frame: Baseline (Day 1) to Day 39
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)
Time frame: 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])
Time frame: Baseline (Day 1) to Day 39
Derived Plasma GSK1278863 Pharmacokinetic Parameter- Maximum Plasma Concentration (Cmax) and Trough Concentration (Ctau)
Time frame: 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])
Time frame: 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)
Time frame: 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
Time frame: 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)

Results and safety

Results posted to the registry on 20 Oct 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GSK1278863	26	23
Placebo	20	19

Primary outcome: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

Time frame: Up to 67 days. Count of participants. Unit: Participants

Measure	GSK1278863 300 mg n = 26	Placebo Matched With GSK1278863 300 mg n = 20	GSK1278863 15 mg n = 23	Placebo Matched With GSK1278863 15 mg n = 19
AE	14	6	9	3
SAE	2	0	0	1

Population analysed: Safety population which comprised of all participants who received at least one dose of study medication.

Primary outcome: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Time frame: Up to 39 days. Count of participants. Unit: Participants

Measure	GSK1278863 300 mg n = 26	Placebo Matched With GSK1278863 300 mg n = 20	GSK1278863 15 mg n = 23	Placebo Matched With GSK1278863 15 mg n = 19
Acute Day 1, Pre-dose; Abnormal NCS	14	16	–	–
Acute Day 1, Pre-dose; Abnormal CS	0	0	–	–
Acute Day 1, 2.5 hour; Abnormal NCS	15	14	–	–
Acute Day 1, 2.5 hour; Abnormal CS	0	0	–	–
Chronic Day 1, Pre-dose; Abnormal NCS	–	–	12	14
Chronic Day 1, Pre-dose; Abnormal CS	–	–	0	0
Chronic Day 1, 2.5 hour; Abnormal NCS	–	–	8	14
Chronic Day 1, 2.5 hour; Abnormal CS	–	–	0	0

Population analysed: Safety Population. Only those participants with data available at the indicated time points were analyzed.

Primary outcome: Number of Participants With Vital Signs of Potential Clinical Importance

Time frame: Up to 39 days. Count of participants. Unit: Participants

Measure	GSK1278863 300 mg n = 26	Placebo Matched With GSK1278863 300 mg n = 20	GSK1278863 15 mg n = 23	Placebo Matched With GSK1278863 15 mg n = 19
Value	3	1	2	3

Population analysed: Safety Population.

Primary outcome: Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance

Time frame: Up to 67 days. Count of participants. Unit: Participants

Measure	GSK1278863 300 mg n = 26	Placebo Matched With GSK1278863 300 mg n = 20	GSK1278863 15 mg n = 23	Placebo Matched With GSK1278863 15 mg n = 19
High Glucose	5	2	5	3
High Calcium	0	0	1	0
High Potassium	1	1	2	1
Low Carbon-dioxide content	0	0	1	1
High Creatinine	1	0	1	0
High Carbon-dioxide content	0	0	0	1

Population analysed: Safety Population.

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 67 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GSK1278863 300 mg	2 of 26 (7.7%)	10 of 26 (38.5%)	0 of 26
Placebo Matched With GSK1278863 300 mg	0 of 20 (0%)	6 of 20 (30%)	0 of 20
GSK1278863 15 mg	0 of 23 (0%)	3 of 23 (13%)	0 of 23
Placebo Matched With GSK1278863 15 mg	1 of 19 (5.3%)	3 of 19 (15.8%)	0 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK1278863 in people with Vascular Disease, Peripheral, run by GlaxoSmithKline at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) (time frame: Up to 67 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02135848.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2017.