Wound Healing
Conditions
Keywords
diabetic foot ulcer, pharmacodynamics, pharmacokinetics, ischemic
Brief 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.
Interventions
DRUGGSK1278863
White to off-white smooth ointment with unit dose strength of 0.05%w/w, 0.1%w/w, 0.5%w/w, 1.0%w/w for topical application as single or repeat doses.
DRUGPlacebo
White to off-white smooth ointment for topical application as single or repeat doses.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
- Healthy Volunteers (Part A Cohort 1) * Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<=1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * \[Single\] corrected QT interval (QTc) \< 450 millisecond (msec). * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and electrocardiogram (ECGs). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with hemoglobin (Hb) values higher than ULN the normal range should always be excluded from enrollment. * Male or female between 18 and 90 years of age inclusive, at the time of signing the informed consent. * A female subject is eligible to participate if she is of non-childbearing potential (postmenopausal or pre-menopausal females with a documented tubal ligation or hysterectomy). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in the protocol. * Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. Inclusion Criteria - DFU Subjects must meet healthy volunteer inclusion criteria and the following * Diagnosed with Type I or Type II diabetes mellitus. * Glycosylated haemoglobin (HbA1c) \<=12%. * QTc \< 480 msec in subjects with bundle branch block. * Lower extremity diabetic foot ulcer of 30 to 364 days' duration. * DFU between 1 centimeter squared (cm \^2) and 20 cm\^2 at screening. * Presence of at least one DFU that meets all of the following criteria: (a). Ulcer has been diagnosed as a full-thickness, neuropathic DFU and is located at or distal to the malleolus (excluding ulcers between the toes but including those of the heel). (b). There is a minimum 2 cm margin between the qualifying study ulcer and any other ulcers on the specified foot. (c). Ulcer size (area) \>=1 cm\^2 and \<=12 cm\^2 (post-debridement at time of randomization). (d). Wagner Grade 1. (e). Depth \<=5 millimeter (mm) with no capsule, tendon or bone exposed and no tunneling, undermining, or sinus tracts. Note: If the subject has more than one qualifying DFU, the ulcer designated as the study ulcer will be at the discretion of the Investigator. Non-study ulcers being treated during the course of the study will be treated with moist wound therapy Standard of Care (SOC) identified under this study. * Adequate vascular perfusion of the affected limb within 30 days of screening, as defined by at least one of the following: (a) Transcutaneous oxygen partial pressure (TcPO2) \>35 millimeter of mercury (mmHg). (b) Ankle-Brachial Index (ABI) \>=0.6 and \<=1.2, confirmed by TcPO2 \>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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose]) | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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; is a congenital anomaly/birth defect; other important medical events; or is associated with liver injury and impaired liver function. |
| Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B) | Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose]) | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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; is a congenital anomaly/birth defect; other important medical events; or is associated with liver injury and impaired liver function. |
| Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A) | Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose]) | ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented. |
| Number of Participants With Clinically Significant 12-lead ECG Measurement Following Repeat Dose Administrations (Part B) | Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose]) | ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented. |
| Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | Day 1 (pre-dose and 48 hours) of Periods 1 and 2 | Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter. |
| Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | Days 1 and 7 (pre-dose), Day 14 (24 hours) | Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter. |
| Number of Participants With Abnormal Nurse/Physician Observation (Part A) | Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose]) | A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed.Since data was not collected, no analysis was performed. |
| Number of Participants With Abnormal Nurse/Physician Observation (Part B) | Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose]) | A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed. Since data was not collected, no analysis was performed. |
| Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Day 1 (pre-dose) | Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, absolute neutrophil count (ANC), monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter. |
| Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B) | Day 1 (pre-dose) | Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, neutrophils, monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter. |
| Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Day 1 (pre-dose and 48 hours) in period 1; Day 1 (48 hours) in period 2 | Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter. |
| Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Days 1 and 7 (pre-dose) and Day 14 (24 hours) | Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter. |
| Maximum Observed Concentration (Cmax) of GSK1278863 (Part A) | Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hrs post-dose | The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification. |
| Cmax of GSK1278863 (Part B) | Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification. |
| Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A) | Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification. |
| Tmax of GSK1278863 (Part B) | Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification. |
| Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A) | Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification. |
| t1/2 of GSK1278863 (Part B) | Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification. |
| Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A) | Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification. |
| Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part B) | Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification. |
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A) | Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification. |
| AUC(0-inf) of GSK1278863 (Part B) | Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification. |
| 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) | Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hrs post-dose | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification. |
| AUC(0-t) of GSK1278863 (Part B) | Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14 | The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification. |
Countries
United States
Participant flow
Recruitment details
This was a randomized, placebo-controlled, single-blind, parallel-group, two part (Part A and Part B) study in healthy volunteers (HVT) and participants with diabetic foot ulcer (DFU).
Pre-assignment details
A total of 65 par. were randomized, however 2 par. did not receive study treatment and were excluded from analysis. All data tables reflect the total of treated par. (63).
Participants by arm
| Arm | Count |
|---|---|
| Placebo HVT (Cohort 1) Cohort 1 comprised of healthy participants. Participants were administered a single dose of placebo on intact skin during two dosing periods. There was a wash out period of at least 10 days between the two periods. | 4 |
| Placebo DFU SD (Cohort 2, 3, 4) Cohorts 2, 3 and 4 consisted of participants with DFU. Participants were administered a single dose of placebo in one (Cohort 3) or two (Cohort 2 and 4) dosing periods. There was a wash out period of at least 10 days between periods. | 3 |
| A/B (Cohort 1) Healthy participants were enrolled. Participants were administered a single dose of treatment A=0.3 milligram (mg) GSK1278863 on intact skin in Period 1 and a single dose of treatment B=3 mg GSK1278863 on intact skin in Period 2. There was a wash out period of 10 days between the two periods. | 9 |
| C/C (Cohort 2) Participants with DFU were administered 0.1 percent of 25 milligrams per square centimeter (mg/cm\^2) GSK1278863 on intact skin in Period 1 followed by a wash-out period of at least 10 days. Participants were then administered a single dose of 0.1 percent of 25 mg/cm\^2 on wounded skin in Period 2. | 5 |
| D (Cohort 3) Participants with DFU were administered a single dose of 1 percent of 25 mg/cm\^2 GSK1278863 on wounded skin. | 5 |
| E/E (Cohort 4) A single dose of 1 percent of 100 mg/cm\^2 GSK1278863 was applied directly to wounded skin in Period 1, followed by application of a single dose of 1 percent of 100 mg/cm\^2 GSK1278863 to intact skin. There was a wash-out period of at least 10 days between the two dosing periods. | 3 |
| Placebo DFU RD (Cohort 5) Participants with DFU received once daily placebo application directly to the wounded skin for 14 days along with standard of care therapy. | 4 |
| R1r (Cohort 5) Participants with DFU received once daily application of 1 percent of 100 mg/cm\^2 GSK1278863 to wounded skin for 14 days along with standard of care treatment. | 26 |
| Sr (Cohort 5) Participants with DFU continued to receive daily application of standard of care wound treatment for 14 days. | 4 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Investigator discretion | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol defined stopping criteria | 1 | 1 | 3 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrew Consent | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo HVT (Cohort 1) | Placebo DFU SD (Cohort 2, 3, 4) | A/B (Cohort 1) | C/C (Cohort 2) | D (Cohort 3) | E/E (Cohort 4) | Placebo DFU RD (Cohort 5) | R1r (Cohort 5) | Sr (Cohort 5) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.5 Years STANDARD_DEVIATION 14.2 | 53.0 Years STANDARD_DEVIATION 8.72 | 44.4 Years STANDARD_DEVIATION 15.27 | 52.6 Years STANDARD_DEVIATION 5.9 | 59.2 Years STANDARD_DEVIATION 7.66 | 48.3 Years STANDARD_DEVIATION 11.93 | 50.0 Years STANDARD_DEVIATION 10.42 | 55.5 Years STANDARD_DEVIATION 6.13 | 55.5 Years STANDARD_DEVIATION 5.26 | 51.2 Years STANDARD_DEVIATION 9.4 |
| Race/Ethnicity, Customized African American/African Heritage (Her.) | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 1 Participants | 16 Participants |
| Race/Ethnicity, Customized Japanese/East Asian Her./South East Asian Her. | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 2 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 19 Participants | 3 Participants | 46 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants | 5 Participants | 5 Participants | 3 Participants | 3 Participants | 23 Participants | 3 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 9 | 0 / 3 | 0 / 5 | 0 / 5 | 0 / 3 | 0 / 4 | 0 / 26 | 0 / 4 |
| other Total, other adverse events | 1 / 4 | 2 / 9 | 1 / 3 | 0 / 5 | 0 / 5 | 1 / 3 | 1 / 4 | 0 / 26 | 1 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 9 | 0 / 3 | 0 / 5 | 0 / 5 | 1 / 3 | 1 / 4 | 0 / 26 | 1 / 4 |
Outcome results
Primary
Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A) | NA Hour |
| A/B (Cohort 1) | Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A) | NA Hour |
| Placebo DFU SD (Cohort 2, 3, 4) | Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A) | NA Hour |
| C (Cohort 2) | Apparent Terminal Elimination Half-life (t1/2) of GSK1278863 (Part A) | NA Hour |
Primary
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A) | NA hour*nanograms/milliliter |
| A/B (Cohort 1) | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A) | NA hour*nanograms/milliliter |
| Placebo DFU SD (Cohort 2, 3, 4) | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A) | NA hour*nanograms/milliliter |
| C (Cohort 2) | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] of GSK1278863 (Part A) | NA hour*nanograms/milliliter |
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)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hrs post-dose
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | 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 hour*nanograms/milliliter |
| A/B (Cohort 1) | 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 hour*nanograms/milliliter |
| Placebo DFU SD (Cohort 2, 3, 4) | 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 hour*nanograms/milliliter |
| C (Cohort 2) | 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 hour*nanograms/milliliter |
Primary
AUC(0-inf) of GSK1278863 (Part B)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | AUC(0-inf) of GSK1278863 (Part B) | NA hour*nanograms/milliliter |
Primary
AUC(0-t) of GSK1278863 (Part B)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | AUC(0-t) of GSK1278863 (Part B) | NA hour*nanograms/milliliter |
Primary
Cmax of GSK1278863 (Part B)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Cmax of GSK1278863 (Part B) | NA ng/mL |
Primary
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A) | NA Hour |
| A/B (Cohort 1) | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A) | NA Hour |
| Placebo DFU SD (Cohort 2, 3, 4) | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A) | NA Hour |
| C (Cohort 2) | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part A) | NA Hour |
Primary
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part B)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) (Part B) | NA Hour |
Primary
Maximum Observed Concentration (Cmax) of GSK1278863 (Part A)
The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hrs post-dose
Population: All participants from whom a PK sample had been obtained and analyzed were included in the PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Maximum Observed Concentration (Cmax) of GSK1278863 (Part A) | NA Nanograms per milliliter (ng/mL) |
| A/B (Cohort 1) | Maximum Observed Concentration (Cmax) of GSK1278863 (Part A) | NA Nanograms per milliliter (ng/mL) |
| Placebo DFU SD (Cohort 2, 3, 4) | Maximum Observed Concentration (Cmax) of GSK1278863 (Part A) | NA Nanograms per milliliter (ng/mL) |
| C (Cohort 2) | Maximum Observed Concentration (Cmax) of GSK1278863 (Part A) | NA Nanograms per milliliter (ng/mL) |
Primary
Number of Participants With Abnormal Nurse/Physician Observation (Part A)
A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed.Since data was not collected, no analysis was performed.
Time frame: Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose])
Population: All Subject Population
Primary
Number of Participants With Abnormal Nurse/Physician Observation (Part B)
A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed. Since data was not collected, no analysis was performed.
Time frame: Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose])
Population: All Subject Population
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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; is a congenital anomaly/birth defect; other important medical events; or is associated with liver injury and impaired liver function.
Time frame: Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose])
Population: All Subject Population comprised of all participants who received at least one dose of study drug (including GSK1278863, placebo and standard care).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | AEs | 2 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | SAEs | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | AEs | 3 Participants |
| A/B (Cohort 1) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | SAEs | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | AEs | 1 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | SAEs | 0 Participants |
| C (Cohort 2) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | AEs | 0 Participants |
| C (Cohort 2) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | SAEs | 0 Participants |
| D (Cohort 3) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | AEs | 2 Participants |
| D (Cohort 3) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | SAEs | 0 Participants |
| E (Cohort 4) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | AEs | 1 Participants |
| E (Cohort 4) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Single Dose Administration (Part A) | SAEs | 1 Participants |
Primary
Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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; is a congenital anomaly/birth defect; other important medical events; or is associated with liver injury and impaired liver function.
Time frame: Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose])
Population: All Subject Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B) | SAEs | 1 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B) | AEs | 2 Participants |
| A/B (Cohort 1) | Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B) | AEs | 5 Participants |
| A/B (Cohort 1) | Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B) | SAEs | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B) | AEs | 2 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With AEs and SAEs Following Repeat Dose Administration (Part B) | SAEs | 1 Participants |
Primary
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A)
Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Time frame: Day 1 (pre-dose and 48 hours) in period 1; Day 1 (48 hours) in period 2
Population: All Subjects Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,high,n=4,3,9,5,5,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,high,n=4,3,8,5,4,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,low,n=4,3,8,5,4,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,high,n=4,1,0,5,0,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,low,n=4,3,9,5,5,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,low,n=4,1,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,low,n=4,3,9,5,5,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,high,n=4,3,8,5,4,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,high,n=4,3,9,5,5,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,low,n=4,1,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,high,n=4,1,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,low,n=4,3,8,5,4,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,high,n=4,3,9,5,5,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,high,n=4,3,8,5,4,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,low,n=4,3,9,5,5,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,low,n=4,3,8,5,4,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,high,n=4,3,8,5,4,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,low,n=4,1,0,5,0,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,high,n=4,1,0,5,0,3 | 1 Participants |
| C (Cohort 2) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,high,n=4,3,9,5,5,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,low,n=4,3,8,5,4,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,low,n=4,3,9,5,5,3 | 0 Participants |
| D (Cohort 3) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,low,n=4,3,8,5,4,3 | 0 Participants |
| D (Cohort 3) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,low,n=4,3,9,5,5,3 | 0 Participants |
| D (Cohort 3) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,high,n=4,3,9,5,5,3 | 1 Participants |
| D (Cohort 3) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,high,n=4,3,8,5,4,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,high,n=4,3,8,5,4,3 | 1 Participants |
| E (Cohort 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,low,n=4,1,0,5,0,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,48 H,low,n=4,3,8,5,4,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,high,n=4,3,9,5,5,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P1,pre-dose,low,n=4,3,9,5,5,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part A) | Glucose,Day1,P2,48 H,high,n=4,1,0,5,0,3 | 2 Participants |
Primary
Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B)
Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Time frame: Days 1 and 7 (pre-dose) and Day 14 (24 hours)
Population: All Subjects Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day1,pre-dose,Low,n=4,26,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day1,pre-dose,High,n=4,26,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day7,pre-dose,Low,n=4,24,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day7,pre-dose,High,n=4,24,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day14,24H,Low,n=3,23,2 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day14,24H,High,n=3,23,2 | 2 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day14,24H,High,n=3,23,2 | 9 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day1,pre-dose,Low,n=4,26,4 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day7,pre-dose,High,n=4,24,4 | 7 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day14,24H,Low,n=3,23,2 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day1,pre-dose,High,n=4,26,4 | 5 Participants |
| A/B (Cohort 1) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day7,pre-dose,Low,n=4,24,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day1,pre-dose,High,n=4,26,4 | 1 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day7,pre-dose,Low,n=4,24,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day14,24H,High,n=3,23,2 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day7,pre-dose,High,n=4,24,4 | 2 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day1,pre-dose,Low,n=4,26,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinical Chemistry Values Outside the Clinical Concern Range (Part B) | Glucose,Day14,24H,Low,n=3,23,2 | 0 Participants |
Primary
Number of Participants With Clinically Significant 12-lead ECG Measurement Following Repeat Dose Administrations (Part B)
ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented.
Time frame: Up to a maximum of 53 days (Start of study treatment through final follow up 2 [28-32 days post last dose])
Population: All Subject Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Clinically Significant 12-lead ECG Measurement Following Repeat Dose Administrations (Part B) | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinically Significant 12-lead ECG Measurement Following Repeat Dose Administrations (Part B) | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinically Significant 12-lead ECG Measurement Following Repeat Dose Administrations (Part B) | 0 Participants |
Primary
Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A)
ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented.
Time frame: Up to a maximum of 75 days (Start of study treatment through final follow up 2 [28-32 days post last dose])
Population: All Subject Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A) | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A) | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A) | 0 Participants |
| C (Cohort 2) | Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A) | 0 Participants |
| D (Cohort 3) | Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A) | 0 Participants |
| E (Cohort 4) | Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Measurement Following Single Dose Administrations (Part A) | 0 Participants |
Primary
Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B)
Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, neutrophils, monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter.
Time frame: Day 1 (pre-dose)
Population: All Subjects Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B) | Lymphocytes, Day 1,pre-dose,Low | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B) | Lymphocytes, Day 1,pre-dose,High | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B) | Lymphocytes, Day 1,pre-dose,Low | 1 Participants |
| A/B (Cohort 1) | Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B) | Lymphocytes, Day 1,pre-dose,High | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B) | Lymphocytes, Day 1,pre-dose,Low | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Hematology Data Outside the Clinical Concern Range (Part B) | Lymphocytes, Day 1,pre-dose,High | 0 Participants |
Primary
Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A)
Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, absolute neutrophil count (ANC), monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter.
Time frame: Day 1 (pre-dose)
Population: All Subjects Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,Low | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,High | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,Low | 1 Participants |
| A/B (Cohort 1) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,High | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,Low | 1 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,High | 0 Participants |
| C (Cohort 2) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,High | 0 Participants |
| C (Cohort 2) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,Low | 0 Participants |
| D (Cohort 3) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,Low | 0 Participants |
| D (Cohort 3) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,High | 0 Participants |
| E (Cohort 4) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,Low | 0 Participants |
| E (Cohort 4) | Number of Participants With Hematology Values Outside the Clinical Concern Range (Part A) | Total ANC,Day 1,pre-dose,High | 0 Participants |
Primary
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B)
Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Time frame: Days 1 and 7 (pre-dose), Day 14 (24 hours)
Population: All Subject Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | DBP,Day 1,pre-dose,Low,n=4,26,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | DBP,Day 1,pre-dose,High,n=4,26,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 1,pre-dose,Low, n=4,26,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 1,pre-dose,High, n=4,26,4 | 1 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 7,pre-dose,Low, n=4,25,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 7,pre-dose,High, n=4,25,4 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 14,24 H,Low, n=3,22,1 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 14,24 H,High, n=3,22,1 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 1,pre-dose,Low, n=4,26,4 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 14,24 H,Low, n=3,22,1 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 1,pre-dose,High, n=4,26,4 | 3 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 7,pre-dose,Low, n=4,25,4 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 7,pre-dose,High, n=4,25,4 | 2 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | DBP,Day 1,pre-dose,Low,n=4,26,4 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | DBP,Day 1,pre-dose,High,n=4,26,4 | 1 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 14,24 H,High, n=3,22,1 | 3 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 1,pre-dose,Low, n=4,26,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | DBP,Day 1,pre-dose,High,n=4,26,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | DBP,Day 1,pre-dose,Low,n=4,26,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 1,pre-dose,High, n=4,26,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 14,24 H,Low, n=3,22,1 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 7,pre-dose,High, n=4,25,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 7,pre-dose,Low, n=4,25,4 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Repeat Dose Administration (Part B) | SBP,Day 14,24 H,High, n=3,22,1 | 0 Participants |
Primary
Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A)
Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Time frame: Day 1 (pre-dose and 48 hours) of Periods 1 and 2
Population: All Subject Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;Low;n=4,3,8,5,4,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;High;n=4,3,8,5,4,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; Low; n=4,1,0,5,0,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;High;n=4,1,0,5,0,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;High;n=4,3,9,5,5,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;Low;n=4,1,0,5,0,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;High;n=4,2,0,5,0,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; High; n=4,1,0,5,0,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;Low;n=4,2,0,5,0,3 | 0 Participants |
| Placebo HVT (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;Low;n=4,3,9,5,5,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;High;n=4,1,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;Low;n=4,1,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;High;n=4,3,8,5,4,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;Low;n=4,3,9,5,5,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;Low;n=4,2,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;High;n=4,2,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; Low; n=4,1,0,5,0,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;High;n=4,3,9,5,5,3 | 0 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; High; n=4,1,0,5,0,3 | 1 Participants |
| A/B (Cohort 1) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;Low;n=4,3,8,5,4,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;Low;n=4,3,9,5,5,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;High;n=4,3,8,5,4,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;Low;n=4,3,8,5,4,3 | 0 Participants |
| Placebo DFU SD (Cohort 2, 3, 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;High;n=4,3,9,5,5,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;High;n=4,3,9,5,5,3 | 2 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;High;n=4,2,0,5,0,3 | 1 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; High; n=4,1,0,5,0,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;Low;n=4,3,9,5,5,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;Low;n=4,2,0,5,0,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; Low; n=4,1,0,5,0,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;Low;n=4,1,0,5,0,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;Low;n=4,3,8,5,4,3 | 0 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;High;n=4,1,0,5,0,3 | 1 Participants |
| C (Cohort 2) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;High;n=4,3,8,5,4,3 | 2 Participants |
| D (Cohort 3) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;High;n=4,3,8,5,4,3 | 0 Participants |
| D (Cohort 3) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;Low;n=4,3,9,5,5,3 | 0 Participants |
| D (Cohort 3) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;High;n=4,3,9,5,5,3 | 1 Participants |
| D (Cohort 3) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;Low;n=4,3,8,5,4,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;Low;n=4,2,0,5,0,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;pre-dose;High;n=4,2,0,5,0,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;High;n=4,3,8,5,4,3 | 1 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;48 hours;Low;n=4,3,8,5,4,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;High;n=4,3,9,5,5,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;Low;n=4,1,0,5,0,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 1; Day 1;pre-dose;Low;n=4,3,9,5,5,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; High; n=4,1,0,5,0,3 | 1 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | DBP Period 2; Day 1; 48 hours; Low; n=4,1,0,5,0,3 | 0 Participants |
| E (Cohort 4) | Number of Participants With Vital Sign Data Outside Clinical Concern Range Following Single Dose Administration (Part A) | SBP; Period 2; Day 1;48 hours;High;n=4,1,0,5,0,3 | 1 Participants |
Primary
t1/2 of GSK1278863 (Part B)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | t1/2 of GSK1278863 (Part B) | NA Hour |
Primary
Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72hrs post-dose
Population: PK population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A) | NA Hour |
| A/B (Cohort 1) | Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A) | NA Hour |
| Placebo DFU SD (Cohort 2, 3, 4) | Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A) | NA Hour |
| C (Cohort 2) | Time of Occurrence of Cmax (Tmax) of GSK1278863 (Part A) | NA Hour |
Primary
Tmax of GSK1278863 (Part B)
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification.
Time frame: Pre-dose and 2 hrs on Day 1 and 7; pre-dose, 1, 2,4, 8, 12 and 24 hrs post-dose on Day 14
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo HVT (Cohort 1) | Tmax of GSK1278863 (Part B) | NA Hour |