3 Month PHI PAD PoM Study

NCT02135848 | Completed Phase 2 Results

• 1 other identifier: 114272
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Vascular Disease, Peripheral

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  Up to 67 days

Secondary Outcomes (16)

• Change From Baseline in Total Number of Contractions to Onset of Claudication

  Baseline (Day 1) to Day 39

• Change From Baseline in Total Work Performed to Onset of Claudication

  Baseline (Day 1) to Day 39

• Change From Baseline in Total Exercise Time to Onset of Claudication

  Baseline (Day 1) to Day 39

• Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance

  Baseline (Day 1) to Day 39

• Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance

  Baseline (Day 1) to Day 39

Study Arms (2)

GSK1278863

EXPERIMENTAL

Study Drug

Drug: GSK1278863

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

GSK1278863 DRUG

GSK1278863

GSK1278863

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (12)

GSK Investigational Site

Palo Alto, California, 94304, United States

Location

GSK Investigational Site

Vista, California, 92083, United States

Location

GSK Investigational Site

Clearwater, Florida, 33761, United States

Location

GSK Investigational Site

Sarasota, Florida, 34239, United States

Location

GSK Investigational Site

Chicago, Illinois, 60612, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46290, United States

Location

GSK Investigational Site

Boone, North Carolina, 28607, United States

Location

GSK Investigational Site

Durham, North Carolina, 27705, United States

Location

GSK Investigational Site

Toledo, Ohio, 43606, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23502, United States

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Peripheral Vascular Diseases

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2012
• First Posted: May 12, 2014
• Study Start: October 15, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: October 20, 2017
• Results First Posted: October 20, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (12)