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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/NCT00935831




Registration number
NCT00935831
Ethics application status
Date submitted
7/07/2009
Date registered
9/07/2009
Date last updated
27/07/2017

Titles & IDs
Public title
Single Dose Safety Study for Compound to Treat Anemia in Patients With Renal Impairment
Scientific title
A Phase I, Single-Dose, Randomized and Single-Blind (Part 1), Fixed Sequence and Open-Label (Part 2), Studyto Evaluate the Safety, Pharmacokinetics, andPharmacodynamics of 1278863A in Subjects With RenalImpairment and Matched Healthy Volunteers
Secondary ID [1] 0 0
112843
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Disease 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease

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

Experimental: Subjects with renal impairment, non-dialysis - Subjects with moderate to severe renal impairment equivalent to National Kidney Foundation Kidney Disease Outcomes Quality Initiative stage 3 and stage 4 who are not undergoing dialysis will be included. Subjects will receive single 50 mg and 150 mg oral doses of GSK1278863A across two dosing periods in a single-blind, randomized sequence. Doses of GSK1278863A will be given as 25 mg and 100 mg tablets, with matching placebo tablets to maintain treatment blinding.

Experimental: Healthy volunteers - Healthy subjects will be matched to the moderate and severe renally impaired subjects for gender, age, and BMI. Subjects will receive single 50 mg and 150 mg oral doses of GSK1278863A across two dosing periods in a single-blind, randomized sequence. Doses of GSK1278863A will be given as 25 mg and 100 mg tablets, with matching placebo tablets to maintain treatment blinding.

Experimental: Hemodialysis dependent subjects - The arm will consist of subjects with severe renal impairment (end-stage renal failure) who have been on stable hemodialysis treatment scheduled three times per week. Subjects will receive single oral doses of 150 mg GSK1278863A in each of 2 dosing periods in an open-label, fixed sequence. GSK1278863A will be administered just prior to receiving scheduled hemodialysis in Dosing Period 1. In Dosing Period 2, subjects will receive a single oral dose of GSK1278863 the morning after completion of a scheduled hemodialysis session.


Treatment: Drugs: GSK1278863A
50mg, 150mg

Treatment: Drugs: Placebo
matching placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AUC (0-24), Cmax, tmax and half-life
Timepoint [1] 0 0
Parts 1&2: Days 1-3
Secondary outcome [1] 0 0
Adverse Events reporting
Timepoint [1] 0 0
throughout study
Secondary outcome [2] 0 0
Safety Labs (Chemistry)
Timepoint [2] 0 0
Screening, Day -1, 2, 3
Secondary outcome [3] 0 0
Safety Labs (Hematology)
Timepoint [3] 0 0
Screening, Days -1, 2, 3
Secondary outcome [4] 0 0
Safety Labs (Urinalysis)
Timepoint [4] 0 0
Screening, Days -1, 2, 3
Secondary outcome [5] 0 0
Vital Signs (blood pressure and heart rate)
Timepoint [5] 0 0
Screening, Days 1, 2, 3
Secondary outcome [6] 0 0
12-lead ECG
Timepoint [6] 0 0
Screening, Day 1
Secondary outcome [7] 0 0
Clinical Monitoring/Observation
Timepoint [7] 0 0
throughout
Secondary outcome [8] 0 0
Actual values, rate of rise, rate of decline and maximum change from baseline in erythropoietin
Timepoint [8] 0 0
Days 1, 2, 3
Secondary outcome [9] 0 0
Actual values, rate of rise, rate of decline and maximum change from baseline in VEGF
Timepoint [9] 0 0
Days 1, 2
Secondary outcome [10] 0 0
Actual values, rate of rise, rate of decline and maximum change from baseline in Hepcidin
Timepoint [10] 0 0
Days 1, 2
Secondary outcome [11] 0 0
Actual values, rate of rise, rate of decline and maximum change from baseline in TIBC (total iron binding capacity)
Timepoint [11] 0 0
Screening, Days 1, 3

Eligibility
Key inclusion criteria
1. A male or female is eligible to enroll and participate in this study if he/she:

- (Part 1) has Moderate to Severe Renal Impairment (equivalent to NKF KDOQI Stage 3
or 4, not receiving dialysis) as determined by estimated Glomerular Filtration
Rate (eGFR) calculated by the abbreviated MDRD equation, OR has Normal Renal
Function determined by creatinine clearance (CLCR) via the Cockcroft-Gault
equation, using serum creatinine and demographic data, obtained at Screening.
Subjects with Normal Renal Function should have no greater than trace blood or
protein on Screening urinalysis.

- (Part 2) has severe renal impairment (end-stage renal failure) and has been on
stable hemodialysis treatment (three times weekly) for 3 months prior to
Screening.

- otherwise healthy or considered clinically stable with respect to underlying
renal impairment as determined by a responsible and experienced physician, based
on a medical evaluation including medical history, physical examination,
laboratory tests and cardiac monitoring.

- has clinical laboratory test results that are considered clinically stable in the
opinion of the Principal Investigator, especially if the clinical abnormality or
laboratory parameter is deemed associated with the subject's underlying renal
impairment. A normal subject with a clinical abnormality or laboratory parameters
outside the reference range may be included only if the Investigator and the
Medical Monitor agree that the finding is unlikely to introduce additional risk
factors and will not interfere with the study procedures.

2. Male or female between 18 and 65 years of age inclusive, at the time of signing the
informed consent.

3. A female subject is eligible to participate if she is of:

- Non-childbearing potential defined as pre-menopausal females with a documented tubal
ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous
amenorrhea [in questionable cases a blood sample with simultaneous follicle
stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is
confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal
status is in doubt will be required to use one of the contraception methods described
in the protocol if they wish to continue their HRT during the study. Otherwise, they
must discontinue HRT to allow confirmation of post-menopausal status prior to study
enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the
cessation of therapy and the blood draw; this interval depends on the type and dosage
of HRT.

Following confirmation of their post-menopausal status, they can resume use of HRT
during the study without use of a contraceptive method.

4. Male subjects must agree to use one of the contraception methods listed in the
protocol. This criterion must be followed from the time of the first dose of study
drug until completion of the Follow-up visit.

5. Body weight greater than or equal to 50 kg and BMI within the range 17 - 33 kg/m2
(inclusive).

6. AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated
bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin
<35%).

7. QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block. These
can be based on single ECG value or average of triplicate values obtained over brief
recording period.

8. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A hemoglobin value at Screening is:

- Healthy male subjects or post-menopausal females: > 16.5 g/dL

- Healthy female subjects: > 15.5 g/dL

- Renally impaired male or female subjects: <10 g/dL

2. The values of hematological parameters at Screening, for healthy subjects only, are
outside the reference range and clinically significant deemed by the Investigator and
Medical Monitor

3. The values of the following tests at Screening, for healthy subjects only, are:

- TIBC: outside the reference range

- Serum iron: outside the reference range

- Serum ferritin: outside the reference range

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

5. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of Screening.

6. A positive test for HIV antibody.

7. A positive pre-study drug/alcohol screen. A minimum list of drugs that will be
screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and
benzodiazepines. A positive pre-study drug screen, for medications that are prescribed
to a subject for pre-existing condition(s), may be allowed if in the opinion of the
Investigator and Medical Monitor the medication will not interfere with the study
procedures or compromise subject safety.

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

9. History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >21 units for males or >14 units for females. One unit is
equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine
or 1 (25 ml) measure of spirits.

10. History of regular use of tobacco- or nicotine-containing in excess of 10 cigarettes
per day or equivalent and an inability to abstain from tobacco or nicotine use from
admission to the clinical research unit until discharge for each dosing period.

11. Use of prescription medication known to be inhibitors of BCRP.

12. Use of non-prescription drugs, including vitamins, herbal and dietary supplements
(including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme
inducer) or 5 half-lives (whichever is longer) prior to the first dose of study drug,
unless in the opinion of the Investigator and Medical Monitor the medication will not
interfere with the study procedures or compromise subject safety.

13. History of sensitivity to any of the study drugs, or components thereof or a history
of drug or other allergy that, in the opinion of the Investigator or Medical Monitor,
contraindicates their participation.

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

15. 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.

16. History of peptic ulcer disease.

17. Subjects with polycystic kidney disease.

18. Post-renal transplantation subjects.

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

20. Pregnant females as determined by positive serum Beta-hCG test at Screening or prior
to dosing.

21. Lactating females.

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

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

24. Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or
pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices of the prohibited
fruits from 7 days prior to the first dose of study drug in Dosing Period 1 until the
collection of the final pharmacokinetic blood sample in Dosing Period 2, unless in the
opinion of the Investigator and Medical Monitor this will not interfere with the study
procedures or compromise subject safety.

25. The subject has participated in a clinical trial and has received an experimental
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).

26. Exposure to more than four experimental investigational products within 12 months
prior to the first dosing day.

27. Subject is mentally or legally incapacitated.

Study design
Purpose of the study
Basic Science
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
12/08/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/04/2010
Sample size
Target
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to characterize the safety and tolerability of single doses of
compound 1278863A in subjects with renal impairment.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00935831
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