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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/NCT01853852




Registration number
NCT01853852
Ethics application status
Date submitted
10/11/2011
Date registered
15/05/2013
Date last updated
18/12/2013

Titles & IDs
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
Secondary ID [1] 0 0
115806
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GR181413A/AT1001 solution
Treatment: Drugs - GR181413A/AT1001 capsule
Other interventions - Potable water
Treatment: Drugs - Placebo capsule

Experimental: 50 mg - GR181413A/AT1001

Experimental: 150 mg - GR181413A/AT1001

Experimental: 450 mg - GR181413A/AT1001

Placebo Comparator: Placebo - placebo


Treatment: Drugs: GR181413A/AT1001 solution
Powder for reconstitution

Treatment: Drugs: GR181413A/AT1001 capsule
Size 2, hard gelatin capsule, white opaque / blue opaque

Other interventions: Potable water
Matched, Size 2, hard gelatin capsule, white opaque/blue opaque

Treatment: Drugs: Placebo capsule
Solution matched
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Profile of plasma pharmacokinetics
Timepoint [1] 0 0
0, 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12h post dose
Primary outcome [2] 0 0
Number of Participants with adverse events
Timepoint [2] 0 0
up to 24 hr
Primary outcome [3] 0 0
Change from baseline in clinical laboratory tests (hematology, chemistry and urinalysis)
Timepoint [3] 0 0
0, 24h post dose
Primary outcome [4] 0 0
Change from baseline in vital signs (blood pressure and heart rate)
Timepoint [4] 0 0
0 ,1 , 2, 3, 4, 5, 6, 24h post dose
Primary outcome [5] 0 0
Change from baseline in 12-lead ECG
Timepoint [5] 0 0
0, i, 2, 3, 6, 24h post dose
Primary outcome [6] 0 0
Profile of urine pharmacokinetics
Timepoint [6] 0 0
0-4, 4-10, 10-12, 12-24h post dose

Eligibility
Key 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.
Minimum age
20 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
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
1/09/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2011
Sample size
Target
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

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

Ethics approval
Ethics application status

Summary
Brief summary
GR181413A/AT1001 (migalastat hydrochloride) is a low molecular weight iminosugar, an analog
of the terminal galactose group that is cleaved from the substrate GL-3. This compound was
researched and developed as a drug for treatment of Fabry disease. This study, MGM115806,
will be the first administration of GR181413A/AT1001 to Japanese subjects to investigate the
safety, tolerability and pharmacokinetics of single oral doses in healthy Japanese adult
subjects. Approximately 12 subjects will receive three treatments of 50, 150 and 450 mg
GR181413A/AT1001 under fasted conditions plus placebo in a dose ascending crossover design.
Serial pharmacokinetic samples will be collected and safety assessments will be performed
following each dose. The pharmacokinetics and dose proportionality of GR181413A/AT1001 after
single oral doses of GR181413A/AT1001 at the dose levels of 50, 150 and 450 mg under fasted
conditions will be assessed.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01853852
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor, Clinical Research
Address 0 0
Amicus Therapeutics
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/NCT01853852