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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/NCT00840320




Registration number
NCT00840320
Ethics application status
Date submitted
9/02/2009
Date registered
10/02/2009
Date last updated
22/06/2017

Titles & IDs
Public title
Repeat Dose Safety Study for Compound to Treat Anemia
Scientific title
A Phase I, Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Repeat Oral Doses of 1278863A in Healthy Subjects
Secondary ID [1] 0 0
112842
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 - 1278863
Treatment: Drugs - Placebo

Experimental: 1 - Repeat doses of active at escalating doses

Placebo Comparator: 2 - Repeat doses of placebo


Treatment: Drugs: 1278863
15mg, 25mg, 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
adverse events reporting
Timepoint [1] 0 0
throughout study
Primary outcome [2] 0 0
Safety Labs (hematology)
Timepoint [2] 0 0
Screening, Days -1, 1-3, 5, 7, 9, 11, 14-18, 21, 25, 28
Primary outcome [3] 0 0
vital signs (blood pressure and heart rate)
Timepoint [3] 0 0
Days 1-15, 28
Primary outcome [4] 0 0
12-lead ECG
Timepoint [4] 0 0
Screening, Days 1-2, 4, 6, 8, 10, 12, 14, 28
Primary outcome [5] 0 0
dual-lead cardiac monitoring (telemetry monitoring)
Timepoint [5] 0 0
Days -1 to 3, 14
Primary outcome [6] 0 0
clinical monitoring/observation
Timepoint [6] 0 0
throughout
Primary outcome [7] 0 0
Safety Labs (Chemistry)
Timepoint [7] 0 0
Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
Primary outcome [8] 0 0
Safety Labs (Urinalysis)
Timepoint [8] 0 0
Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
Secondary outcome [1] 0 0
AUC(0-8) on Day 1, AUC(0-t), Cmax, tmax and t1/2, on Days 1 and 14
Timepoint [1] 0 0
Days 1-2, 4, 6, 8, 10, 12, 14-18
Secondary outcome [2] 0 0
Trough plasma concentrations at the end of the dosing interval
Timepoint [2] 0 0
Days 2, 4, 6, 8, 10 and 12
Secondary outcome [3] 0 0
Hemoglobin actual values, rate of rise, maximum change from baseline, and rate of decline following stopping of dosing
Timepoint [3] 0 0
Days 1, 7, 14, 21, 28
Secondary outcome [4] 0 0
Fetal hemoglobin actual values, change from baseline, and percent of total hemoglobin
Timepoint [4] 0 0
Days 1, 7, 14, 21, 28
Secondary outcome [5] 0 0
Actual values and change from baseline in erythropoietin
Timepoint [5] 0 0
Days 1-4, 7, 14-15, 18, 21
Secondary outcome [6] 0 0
Actual values and change from baseline in absolute VEGF
Timepoint [6] 0 0
Days 1-2, 14-15, 18, 21
Secondary outcome [7] 0 0
Actual values and change from baseline in hepcidin
Timepoint [7] 0 0
Days 1-2, 7, 14-15, 18, 21
Secondary outcome [8] 0 0
Actual values and change from baseline in total iron binding capacity (TIBC)
Timepoint [8] 0 0
Screening, Days 1, 7, 14, 18, 21
Secondary outcome [9] 0 0
Actual values and change from baseline in transferring saturation (%)
Timepoint [9] 0 0
Days 1, 7, 14, 18, 21

Eligibility
Key inclusion criteria
1. Healthy as determined by a responsible physician, based on a medical evaluation
including medical history, physical examination, laboratory tests and cardiac
monitoring.

2. Male or female between 18 and 55 years of age, inclusive.

3. A female subject must be of non-childbearing potential.

4. Male subjects must agree to use one of the acceptable contraception methods listed in
the protocol

5. Body weight greater than or equal to 50 kg and BMI within the range 19 - 31 kg/m2
(inclusive).

6. Capable of giving written informed consent

7. QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. The subject has a positive pre-study drug screen.

2. A hemoglobin value at screening is:

- Male subjects or post-menopausal females: > 15.5 g/dL

- Female subjects: > 14.5 g/dL

3. The values of hematological parameters at screening are:

MCV: outside the reference range and clinically significant deemed by the investigator
and GSK Medical Monitor

4. The values of the following tests at screening are:

- TIBC: outside the reference range

- Serum iron: outside the reference range

- Serum ferritin: outside the reference range

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

6. Clinically significant abnormal CPK determined by the investigator and GSK Medical
Monitor.

7. Calculated creatinine clearance: < 60mL/min

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

9. A positive test for HIV antibody.

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

11. History of regular alcohol consumption within 6 months of the study

12. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 6 months prior to screening.

13. 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 drug

14. 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 GSK Medical
Monitor, contraindicates their participation.

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

16. 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.

17. History of peptic ulcer disease.

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

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

20. Lactating females.

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

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

23. Consumption of red wine, seville oranges, grapefruit or grapefruit juice, exotic
citrus fruits, grapefruit hybrids or fruit juices of the prohibited fruits from 7 days
prior to the first dose of study medication

24. 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).

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

26. 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
Parallel
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
13/03/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/09/2009
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

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 repeat doses of
compound 1278863A in healthy subjects.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00840320
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/NCT00840320