A Phase I, Randomized, Single-Blind, Four-Period Cross-Over, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of GR181413A/AT1001 in Healthy Japanese Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01853852
• Date of registration: 10/11/2011
• Prospective Registration: No
• Primary sponsor: Amicus Therapeutics
• Public title: A Phase I, Randomized, Single-Blind, Four-Period Cross-Over, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of GR181413A/AT1001 in Healthy Japanese Subjects
• Scientific title: A Phase I, Randomized, Single-Blind, Four-Period Cross-Over, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of GR181413A/AT1001 in Healthy Japanese Subjects
• Date of first enrolment: September 2011
• Target sample size: 14
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01853852
• Study type: Interventional
• Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject)
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Medical Monitor, Clinical Research
• Affiliation: Amicus Therapeutics

Key inclusion & exclusion criteria

Inclusion Criteria:

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

2. Male or female between 20 and 55 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 female.

4. Male subjects with female partners of child-bearing potential must agree to use one
of the contraception methods. This criterion must be followed from the time of the
first dose of study medication until 5 terminal half-lives post-last dose.

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

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

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

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

9. 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.

Exclusion Criteria:

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

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

3. A positive test for HIV antibody.

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

5. 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 longest).

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

7. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St Johns 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.

8. 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.

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

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

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

12. Lactating females.

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

14. Subject is mentally or legally incapacitated.



Age minimum: 20 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Fabry Disease

Intervention(s)

Drug: GR181413A/AT1001 solution

Drug: GR181413A/AT1001 capsule

Other: Potable water

Drug: Placebo capsule

Primary Outcome(s)

Change from baseline in clinical laboratory tests (hematology, chemistry and urinalysis) [Time Frame: 0, 24h post dose]

Profile of plasma pharmacokinetics [Time Frame: 0, 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12h post dose]

Change from baseline in 12-lead ECG [Time Frame: 0, i, 2, 3, 6, 24h post dose]

Profile of urine pharmacokinetics [Time Frame: 0-4, 4-10, 10-12, 12-24h post dose]

Change from baseline in vital signs (blood pressure and heart rate) [Time Frame: 0 ,1 , 2, 3, 4, 5, 6, 24h post dose]

Number of Participants with adverse events [Time Frame: up to 24 hr]

Secondary ID(s)

115806

Source(s) of Monetary Support

Please refer to primary and secondary sponsors