Phase 1 N=63 Randomized Single-blind Treatment

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Single and Repeated Doses of Topical GSK1278863

Wound Healing

Bottom Line

View on ClinicalTrials.gov: NCT01831804 ↗

Enrolled (actual)

Serious AEs

4.8%

Results posted

Aug 2019

Primary outcome: Primary: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) — 2; 3; 1; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: GSK1278863 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Feb 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A)	2; 3; 1; 0; 2; 1	—
PRIMARY Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B)	2; 5; 2; 1; 0; 1	—
PRIMARY Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A)	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Clinically Significant 12-lead ECG Measurement Following Repeat Dose Administrations (Part B)	0; 0; 0	—
PRIMARY Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)	0; 0; 0; 0; 0; 1	—
PRIMARY Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)	0; 0; 0; 0; 1; 0	—
PRIMARY Number of Participants With Abnormal Nurse/Physician Observation (Part A)	—	—
PRIMARY Number of Participants With Abnormal Nurse/Physician Observation (Part B)	—	—
PRIMARY Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A)	0; 1; 1; 0; 0; 0	—
PRIMARY Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B)	0; 1; 0; 0; 0; 0	—
PRIMARY Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)	0; 0; 0; 0; 5; 1	—
PRIMARY Maximum Observed Concentration (Cmax) of GSK1278863 (Part A)	NA; NA; NA; NA	—
PRIMARY Cmax of GSK1278863 (Part B)	NA	—
PRIMARY Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A)	NA; NA; NA; NA	—
PRIMARY Tmax of GSK1278863 (Part B)	NA	—
PRIMARY Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A)	NA; NA; NA; NA	—
PRIMARY t1/2 of GSK1278863 (Part B)	NA	—
PRIMARY Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A)	NA; NA; NA; NA	—
PRIMARY Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part B)	NA	—
PRIMARY Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A)	NA; NA; NA; NA	—
PRIMARY AUC(0-inf) of GSK1278863 (Part B)	NA	—
PRIMARY Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments [AUC(0-t)] of GSK1278863 (Part A)	NA; NA; NA; NA	—
PRIMARY AUC(0-t) of GSK1278863 (Part B)	NA	—

Summary

This is a randomized, placebo-controlled, single-blind (subjects and investigators will be blinded, GSK internal personnel will not be blinded), parallel-group, two part (Part A, Part B) trial in healthy volunteers and subjects with diabetic foot ulcers. Part A is designed to evaluate single applications of GSK1278863 in one cohort of healthy volunteers (intact skin) and approximately 3 cohorts of diabetic subjects. Part B is designed to evaluate first single, and then repeat applications of GSK1278863 in diabetics, both in the clinic and by subjects at home. Part B will include approximately 3 cohorts in which the concentration of drug applied will be determined by pharmacokinetic data from Part A and earlier cohorts in Part B.

Eligibility Criteria

Inclusion Criteria - Healthy Volunteers (Part A Cohort 1)

Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =1 cm^2 and 35 millimeter of mercury (mmHg). (b) Ankle-Brachial Index (ABI) >=0.6 and 35 mmHg. (c) Toe pressure (plethysmography) >50 mmHg. (d) Doppler ultrasound (biphasic or triphasic waveforms) consistent with adequate blood flow to the affected extremity, as determined by SOC.

Exclusion Criteria - Healthy Volunteers (Part A Cohort 1)

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).
History of malignancy within 5 years of Screening or those with a strong family history of cancer (e.g., familial cancer disorders), with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated.
A history of drug or alcohol abuse, or a history of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mililiter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
A positive test for human immunodeficiency virus (HIV) antibody.
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 (whichever is longer).
Unable to refrain from the use of prescription or 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 medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
History of sensitivity to any of the study medications, 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.
Where participation in the study would result in donation of blood or blood products in excess of 500mL within a 56 day period.
Pregnant females as determined by positive urine human chorionic gonadotropin test at screening or prior to dosing.
Unwillingness or inability to follow the procedures outlined in the protocol.
Subject is mentally or legally incapacitated. Exclusion Criteria - DFU Subjects

Healthy volunteer exclusions apply to DFU subjects in addition to the following:

Subjects with ulcers accompanied by infected cellulitis, osteomyelitis, or clinical signs or symptoms of infection, Gangrene on any part of affected limb, Active Charcot's foot on the study limb, Planned vascular surgery, angioplasty or thrombolysis, Ulcers involving exposure of tendon, bone, or joint capsule (It is acceptable to have ulcers extending through the dermis and into subcutaneous tissue with presence of granulation tissue), Ulcers due to non-diabetic etiology.
Any unstable vascular syndromes (such as transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, acute myocardial infarction (MI) or acute coronary syndrome event (ACS) and/or any major changes (per investigator's judgment) to related medications within 6 months prior to randomization.
History or malignancy within 5 years of screening or those with a strong family history of cancer (e.g. familial cancer disorders), with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated.
Other clinically significant cardiovascular, pul

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01831804). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.