Last updated: 11/07/2018 09:52:27
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
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official 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
Trial description: 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.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
Profile of plasma pharmacokinetics
Timeframe: 0, 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12h post dose
Number of Participants with adverse events
Timeframe: up to 24 hr
Change from baseline in clinical laboratory tests (hematology, chemistry and urinalysis)
Timeframe: 0, 24h post dose
Change from baseline in vital signs (blood pressure and heart rate)
Timeframe: 0 ,1 , 2, 3, 4, 5, 6, 24h post dose
Change from baseline in 12-lead ECG
Timeframe: 0, i, 2, 3, 6, 24h post dose
Profile of urine pharmacokinetics
Timeframe: 0-4, 4-10, 10-12, 12-24h post dose
Secondary outcomes:
Not applicable
Interventions:
Enrollment:
14
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Hiroko Ino, Naoki Takahashi, Takumi Terao, Paul N Mudd Jr. Phase I Randomized, Dose-Escalation Pharmacokinetic Study of Single-Dose Migalastat Hydrochloride (GR181413A/AT1001) in Healthy Japanese Subjects. J Drug Asses. 2013;2(0):87-93.
Medical condition
Fabry disease
Product
migalastat
Collaborators
Not applicable
Study date(s)
September 2011 to December 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
20 - 55 Years
Accepts healthy volunteers
yes
- 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.
- 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.
Inclusion and 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.
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2011-19-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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