A Study to Assess the Relative Bioavailability of Four New Formulations of GSK1605786 in Healthy Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01114607
• Date of registration: 29/04/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Assess the Relative Bioavailability of Four New Formulations of GSK1605786 in Healthy Subjects
• Scientific title: A Single Dose, Randomized, Five-Period Crossover Study to Assess the Relative Bioavailability of Four New Formulations of the CCR9 Receptor Antagonist GSK1605786A (CCX282) in Healthy Male and Female Subjects
• Date of first enrolment: May 5, 2010
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01114607
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Single Group Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

1. AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is
acceptable if bilirubin is fractionated and direct bilirubin <35%).

2. Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and ECG.
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 GSK Medical Monitor agree that the finding is unlikely to introduce additional
risk factors and will not interfere with the study procedures.

3. Male or female between 18 and 55 years of age inclusive, at the time of signing the
informed consent.

4. 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 in Section 8.1 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.

- Child-bearing potential and agrees to use one of the contraception methods listed
in Section 8.1 for an appropriate period of time (as determined by the product
label or investigator) prior to the start of dosing to sufficiently minimize the
risk of pregnancy at that point. Female subjects must agree to use contraception
until 4 weeks post-last dose.

5. Male subjects must agree to use one of the contraception methods listed in Section
8.1. This criterion must be followed from the time of the first dose of study
medication until 4 weeks post-last dose.

6. Body weight = 50 kg (110lbs) for men and =45 kg (99 lbs) for women, and BMI within the
range 18.5 - 31 kg/m2 (inclusive).

7. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

8. 12-lead ECG without any clinically significant abnormality as judged by the
Investigator, and average QTcB or QTcF < 450 msec or QTc < 480 msec in subjects with
Bundle Branch Block.

9. Able to complete all study procedures and planned treatment periods.

Exclusion Criteria:

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

2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

3. Known celiac disease and positive serologic testing for anti-tTG antibodies (required
to screen for undiagnosed celiac disease)

4. A positive pre-study drug/alcohol screen.

5. A positive test for HIV antibody.

6. 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 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of
wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.

7. Unwilling to abstain from alcohol for 48 hours prior to screening, and 48 hours prior
to the start of dosing until collection of the final pharmacokinetic sample during
each treatment period.

8. 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).

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

10. 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.

11. History of sensitivity to the study medication, 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.

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

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

14. Lactating females.

15. The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic
blood pressure is outside the range of 45-90mmHg, or heart rate is outside the range
of 50-100bpm for female subjects or 45-100 bpm for male subjects at Screening and
pre-dose on Day 1.

16. Unwillingness or inability to follow the procedures outlined in the protocol.

17. Subject is mentally or legally incapacitated.

18. Subject with a medical condition which in the opinion of the investigator and GSK
Medical Monitor makes them unsuitable for the study.

19. History of sensitivity to heparin or heparin-induced thrombocytopenia.

20. History of regular use of tobacco- or nicotine-containing products within 6 months
prior to screening and unwilling to remain abstinent from tobacco or nicotine
containing products for the duration of the study.

21. Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pomegranate,
and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days
prior to the first dose of study medication.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn's Disease

Intervention(s)

Drug: GSK1605786 ChemoCentryx: formulation A

Drug: GSK1605786 GSK: formulation B

Drug: GSK1605786 GSK tablet: formulation E

Drug: GSK1605786 GSK modified-process: formulation D

Drug: GSK1605786 GSK direct-fill: formulation C

Primary Outcome(s)

Plasma GSK1605786 parameters: AUC(0-8), AUC(0-t), Cmax. [Time Frame: 2-4 weeks after the last subject last visit]

Secondary Outcome(s)

Plasma GSK1605786 parameters: AUC(0-24), %AUCex, tlag, tmax, t1/2 [Time Frame: 2-4 weeks after the last subject last visit]

Safety and tolerability parameters including vital signs, ECGs, clinical laboratory [Time Frame: Results will be monitered in real time from screening through to the follow-up visit]

Secondary ID(s)

114203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors