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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02348372




Registration number
NCT02348372
Ethics application status
Date submitted
5/04/2012
Date registered
28/01/2015
Date last updated
22/06/2017

Titles & IDs
Public title
Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1278863A in Healthy Subjects
Scientific title
A Phase I, Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation (Part 1), Fixed Sequence and Open-Label (Part 2), Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1278863A in Healthy Subjects
Secondary ID [1] 0 0
115385
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaemia 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK1278863A Placebo
Treatment: Drugs - GSK1278863A

Placebo Comparator: GSK1278863A Placebo - 5, 25 and 100 mg matched

Experimental: GSK1278863A 10mg - A round, biconvex, white film coated tablet

Experimental: GSK1278863A 25mg - A round, biconvex, white film coated tablet

Experimental: GSK1278863A 50mg - A round, biconvex, white film coated tablet

Experimental: GSK1278863A 100mg - A round, biconvex, white film coated tablet


Treatment: Drugs: GSK1278863A Placebo
Matching size, shape and color

Treatment: Drugs: GSK1278863A
A round, biconvex, white film coated tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Timepoint [1] 0 0
up to 96 hr
Primary outcome [2] 0 0
AUC(0-t), AUC(0-8), Cmax, tmax and t½ of GSK1278863A
Timepoint [2] 0 0
up to 96 hr
Primary outcome [3] 0 0
Changes from Baseline of Clinical laboratory tests
Timepoint [3] 0 0
0,2448 and 96 hr
Primary outcome [4] 0 0
Changes from Baseline of Vital signs
Timepoint [4] 0 0
0, 1,2,3,4,8 and 24hr
Primary outcome [5] 0 0
Change from Baseline of 12-lead ECG
Timepoint [5] 0 0
0,4 and 8 hr
Secondary outcome [1] 0 0
Hemoglobin endpoints: Hemoglobin actual values, change from baseline, rate of rise/decline, maximum change from baseline, and maximum % change from baseline
Timepoint [1] 0 0
up to 96 hr

Eligibility
Key inclusion criteria
- AST, ALT, alkaline phosphatase and bilirubin >1.5xULN.

- Healthy Male or female between 20 and 65 years of age inclusive, at the time of
signing the informed consent.

- Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods.

- Body weight > 50 kg and BMI within the range 18.5 - 29.0 kg/m2 (inclusive).

- Capable of giving written informed consent.

- QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

- Japanese defined being born in Japan, having four ethnic Japanese grandparents,
holding a Japanese passport or identity papers and being able to speak Japanese.
Japanese subjects should be also have lived outside Japan for less than 10 years.

- Caucasian, defined as an individual having four grandparents who are all descendents
of the original peoples of Europe.
Minimum age
20 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- A positive pre-study drug screen. A minimum list of drugs that will be screened for
include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines

- A hemoglobin value at Screening is of: Healthy male subjects or post-menopausal
females: > 16.5 g/dL, Healthy female (non-childbearing potential) subjects: > 15.5
g/dL

- The values of hematological parameters at screening are: MCV: outside the reference
range and deemed clinically significant by the investigator and GSK Medical Monitor.

- The values of the following tests at Screening, for healthy subjects are: TIBC:
outside the reference range of the population being studied, Serum iron: outside the
reference range of the population being studied, Serum ferritin: outside the reference
range of the population being studied

- A value at screening is greater than the upper limit of reference range for the
following clinical laboratory parameters: AST, ALT, direct bilirubin.

- Clinically significant abnormal CPK determined by the Investigator and GSK Medical
Monitor.

- Calculated creatinine clearance: < 80 mL/min

- A positive test for HIV antibody

- History of drug abuse or dependence within 6 months of the study.

- History of regular alcohol consumption within 6 months of the study

- History or regular use of tobacco- or nicotine-containing products within 6 months
prior to screening.

- 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 GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
subject safety. By exception, subject may take acetaminophen (<2 grams/day) up to 48
hours prior to the first dose of study drug.

- 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.

- History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical
research unit uses heparin to maintain intravenous cannula).

- Subjects with a pre-existing condition interfering with normal gastrointestinal
anatomy or motility, and/or hepatic function that could interfere with the absorption,
metabolism, and/or excretion of the study drugs. Examples of conditions that could
interfere with normal gastrointestinal anatomy or motility include cholecystectomy,
gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection,
vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue.
Examples of conditions that could interfere with hepatic function include Gilberts
syndrome.

- History of peptic ulcer disease or chronic rectal bleeding.

- History of malignancy. Non-melanoma skin cancer that has been definitely removed is
allowed.

- Subjects with a baseline medical history of proliferative diabetic retinopathy,
preproliferative diabetic retinopathy, or wet age-related macular degeneration (AMD).

- Pregnant females as determined by positive serum or urine hCG test at screening or
prior to dosing.

- Lactating females.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Unwillingness or inability to follow the procedures, or lifestyle and/or dietary
restrictions outlined in the protocol.

- Consumption of >3 servings per day of red wine, grapefruit (juice), blood orange
(juice), star fruit, onions, kale, broccoli, green beans, or apples from 7 days prior
to the first dose of investigational product, unless in the opinion of the
Investigator and GSK Medical Monitor this will not interfere with the study procedures
and compromise subject safety.

- 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 or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Subject is mentally or legally incapacitated.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/03/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/06/2011
Sample size
Target
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick, Sydney
Recruitment postcode(s) [1] 0 0
2031 - Randwick, Sydney

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
GSK1278863A is a novel small molecule agent, which stimulates erythropoiesis through
inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs). This compound is
being developed for the treatment of anemia. This study, PHI115385, will be the first
administration of GSK1278863A to Japanese subjects to investigate the safety, tolerability,
pharmacokinetics, and pharmacodynamics of single oral doses in healthy Japanese adult
subjects. Healthy Caucasian adult subjects will be included in order to compare
pharmacokinetics of GSK1278863A and its metabolite(s), and pharmacodynamics of GSK1278863A.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02348372
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02348372