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

NCT01114607 | Completed Phase 1

• 1 other identifier: 114203
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single dose, randomized, five-period, crossover study in healthy volunteers to assess the relative bioavailability of four GSK developed oral formulations of GSK1605786 relative to the capsule formulation administered in the ChemoCentryx Phase IIb, PROTECT-1 Study and ChemoCentryx Thorough QT/QTc Study. Approximately 24 subjects will be randomized to receive a single 500 mg dose of each of the five formulations of GSK1605786 after a standard breakfast. Serial pharmacokinetic samples will be collected following each dose and safety assessments will be performed. The relative bioavailability of the GSK capsule formulation will be compared to the ChemoCentryx formulation while the relative bioavailability the three other formulations will be compared to the GSK capsule formulation intended for use in a GlaxoSmithKline Phase IIb study.

Conditions

Crohn's Disease

Keywords

GSK1605786; relative bioavailability; CCR9 receptor antagonist

Outcome Measures

Primary Outcomes (1)

• Plasma GSK1605786 parameters: AUC(0-∞), AUC(0-t), Cmax.

  2-4 weeks after the last subject last visit

Secondary Outcomes (2)

• Plasma GSK1605786 parameters: AUC(0-24), %AUCex, tlag, tmax, t1/2

  2-4 weeks after the last subject last visit

• Safety and tolerability parameters including vital signs, ECGs, clinical laboratory

  Results will be monitered in real time from screening through to the follow-up visit

Study Arms (12)

Treatment sequence ABCDE

EXPERIMENTAL

Eligible subjects will be randomized in sequence ABCDE and will receive: A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, and E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence ABDEC

EXPERIMENTAL

Eligible subjects will be randomized in sequence ABDEC and will receive: A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily, and C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence ABECD

EXPERIMENTAL

Eligible subjects will be randomized in sequence ABECD and will receive: A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, and D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence ABCED

EXPERIMENTAL

Eligible subjects will be randomized in sequence ABCED and will receive: A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, E= a film coated tablet of GSK1605786 GSK formulation 500 mg once daily and D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence ABDCE

EXPERIMENTAL

Eligible subjects will be randomized in sequence ABDCE and will receive: A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, and E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence ABEDC

EXPERIMENTAL

Eligible subjects will be randomized in sequence ABEDC and will receive: A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, and C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence BACDE

EXPERIMENTAL

Eligible subjects will be randomized in sequence BACDE and will receive: B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, and E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence BADEC

EXPERIMENTAL

Eligible subjects will be randomized in sequence BADEC and will receive: B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily, and C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence BAECD

EXPERIMENTAL

Eligible subjects will be randomized in sequence BAECD and will receive: B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, and D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence BACED

EXPERIMENTAL

Eligible subjects will be randomized in sequence BACED and will receive: B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily, and D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence BADCE

EXPERIMENTAL

Eligible subjects will be randomized in sequence BADCE and will receive: B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily, and E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Treatment sequence BAEDC

EXPERIMENTAL

Eligible subjects will be randomized in sequence BAEDC and will receive: B= two capsules of GSK1605786 GSK formulation 250 milligrams once daily, A= two capsules of GSK1605786 ChemoCentryx formulation 250 milligrams once daily, E= film coated tablet of GSK1605786 GSK formulation 500 mg once daily, D= two capsules of GSK1605786 GSK modified-process formulation 250 milligrams once daily, and C= two capsules of GSK1605786 GSK direct-fill formulation 250 milligrams once daily.

Drug: GSK1605786 ChemoCentryx: formulation A; Drug: GSK1605786 GSK: formulation B; Drug: GSK1605786 GSK direct-fill: formulation C; Drug: GSK1605786 GSK modified-process: formulation D; Drug: GSK1605786 GSK tablet: formulation E

Interventions

GSK1605786 ChemoCentryx: formulation A DRUG

ChemoCentryx formulation A will be an opaque Swedish orange body, blue coloured capsule with size zero, administered 30 minutes after standard breakfast.

Treatment sequence ABCDE; Treatment sequence ABCED; Treatment sequence ABDCE; Treatment sequence ABDEC; Treatment sequence ABECD; Treatment sequence ABEDC; Treatment sequence BACDE; Treatment sequence BACED; Treatment sequence BADCE; Treatment sequence BADEC; Treatment sequence BAECD; Treatment sequence BAEDC

GSK1605786 GSK: formulation B DRUG

GSK1605786 formulation B will be an opaque Swedish orange body capsule with size 0, administered 30 minutes after standard breakfast.

Treatment sequence ABCDE; Treatment sequence ABCED; Treatment sequence ABDCE; Treatment sequence ABDEC; Treatment sequence ABECD; Treatment sequence ABEDC; Treatment sequence BACDE; Treatment sequence BACED; Treatment sequence BADCE; Treatment sequence BADEC; Treatment sequence BAECD; Treatment sequence BAEDC

GSK1605786 GSK direct-fill: formulation C DRUG

GSK1605786 formulation C will be an opaque Swedish orange body capsule with size 1, administered 30 minutes after standard breakfast.

Treatment sequence ABCDE; Treatment sequence ABCED; Treatment sequence ABDCE; Treatment sequence ABDEC; Treatment sequence ABECD; Treatment sequence ABEDC; Treatment sequence BACDE; Treatment sequence BACED; Treatment sequence BADCE; Treatment sequence BADEC; Treatment sequence BAECD; Treatment sequence BAEDC

GSK1605786 GSK modified-process: formulation D DRUG

GSK1605786 formulation D will be an opaque Swedish orange body capsule with size 0, administered 30 minutes after standard breakfast.

Treatment sequence ABCDE; Treatment sequence ABCED; Treatment sequence ABDCE; Treatment sequence ABDEC; Treatment sequence ABECD; Treatment sequence ABEDC; Treatment sequence BACDE; Treatment sequence BACED; Treatment sequence BADCE; Treatment sequence BADEC; Treatment sequence BAECD; Treatment sequence BAEDC

GSK1605786 GSK tablet: formulation E DRUG

GSK1605786 formulation D will be a pink coloured film coated tablet, administered 30 minutes after standard breakfast.

Treatment sequence ABCDE; Treatment sequence ABCED; Treatment sequence ABDCE; Treatment sequence ABDEC; Treatment sequence ABECD; Treatment sequence ABEDC; Treatment sequence BACDE; Treatment sequence BACED; Treatment sequence BADCE; Treatment sequence BADEC; Treatment sequence BAECD; Treatment sequence BAEDC

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• 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.
• Male or female between 18 and 55 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 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.
• 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.
• 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).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• 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.
• Able to complete all study procedures and planned treatment periods.

You may not qualify if:

• 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).
• Known celiac disease and positive serologic testing for anti-tTG antibodies (required to screen for undiagnosed celiac disease)
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• 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.
• 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.
• 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.
• 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.
• 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.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Pregnant females as determined by positive serum hCG test at screening or urine hCG test prior to dosing.
• Lactating females.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Buffalo, New York, 14202, United States

Location

Related Links

• Results for study 114203 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2010
• First Posted: May 3, 2010
• Study Start: May 5, 2010
• Primary Completion: June 29, 2010
• Study Completion: June 29, 2010
• Last Updated: July 18, 2017

Record last verified: 2017-07

Locations

US (1)