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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01853852
Recruitment Status : Completed
First Posted : May 15, 2013
Last Update Posted : December 18, 2013
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

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.

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: GR181413A/AT1001 solution Drug: GR181413A/AT1001 capsule Other: Potable water Drug: Placebo capsule Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
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
Study Start Date : September 2011
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2011


Arm Intervention/treatment
Experimental: 50 mg
GR181413A/AT1001
Drug: GR181413A/AT1001 solution
Powder for reconstitution

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

Drug: Placebo capsule
Solution matched

Experimental: 150 mg
GR181413A/AT1001
Drug: GR181413A/AT1001 capsule
Size 2, hard gelatin capsule, white opaque / blue opaque

Experimental: 450 mg
GR181413A/AT1001
Drug: GR181413A/AT1001 capsule
Size 2, hard gelatin capsule, white opaque / blue opaque

Placebo Comparator: Placebo
placebo
Drug: GR181413A/AT1001 solution
Powder for reconstitution

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

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

Drug: Placebo capsule
Solution matched




Primary Outcome Measures :
  1. Profile of plasma pharmacokinetics [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12h post dose ]
    AUC, Cmax, tmax, Tlast , t1/2, CL/F, Vz/F

  2. Number of Participants with adverse events [ Time Frame: up to 24 hr ]
  3. Change from baseline in clinical laboratory tests (hematology, chemistry and urinalysis) [ Time Frame: 0, 24h post dose ]
  4. Change from baseline in vital signs (blood pressure and heart rate) [ Time Frame: 0 ,1 , 2, 3, 4, 5, 6, 24h post dose ]
  5. Change from baseline in 12-lead ECG [ Time Frame: 0, i, 2, 3, 6, 24h post dose ]
  6. Profile of urine pharmacokinetics [ Time Frame: 0-4, 4-10, 10-12, 12-24h post dose ]
    Ae, CLr, %Fx



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Ages Eligible for Study:   20 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01853852


Locations
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Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Sponsors and Collaborators
Amicus Therapeutics
Investigators
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Study Director: Medical Monitor, Clinical Research Amicus Therapeutics
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT01853852    
Other Study ID Numbers: 115806
First Posted: May 15, 2013    Key Record Dates
Last Update Posted: December 18, 2013
Last Verified: December 2013
Additional relevant MeSH terms:
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Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
1-Deoxynojirimycin
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action