Fabry DiseasePhase 1NCT01853852
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
A Phase 1 study testing GR181413A/AT1001 solution, GR181413A/AT1001 capsule and Potable water in people with Fabry Disease, run by Amicus Therapeutics at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Fabry Disease
- What is being tested?
- GR181413A/AT1001 solution, GR181413A/AT1001 capsule and Potable water
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteAustralia
- Study dates
- Sep 2011to Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
- Male or female between 20 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 female.
- 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.
- Body weight >=50 kg and BMI within the range 18.5 - 29.0 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
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- AST, ALT, alkaline phosphatase and bilirubin > 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Single QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
- 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.
Who cannot join
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study
- 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).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
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- 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.
- 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.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Fabry Disease
- Being tested
- GR181413A/AT1001 solution, GR181413A/AT1001 capsule, Potable water, Placebo capsule
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GR181413A/AT1001 solutionDrug
Powder for reconstitution
GR181413A/AT1001 capsuleDrug
Size 2, hard gelatin capsule, white opaque / blue opaque
Potable waterOther
Matched, Size 2, hard gelatin capsule, white opaque/blue opaque
Placebo capsuleDrug
Solution matched
| Study group | Role | What they receive |
|---|---|---|
| 50 mg | Experimental | GR181413A/AT1001 Receives: Drug: GR181413A/AT1001 solution; Other: Potable water; Drug: Placebo capsule |
| 150 mg | Experimental | GR181413A/AT1001 Receives: Drug: GR181413A/AT1001 capsule |
| 450 mg | Experimental | GR181413A/AT1001 Receives: Drug: GR181413A/AT1001 capsule |
| Placebo | Placebo comparator | placebo Receives: Drug: GR181413A/AT1001 solution; Drug: GR181413A/AT1001 capsule; Other: Potable water; Drug: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Profile of plasma pharmacokinetics
AUC, Cmax, tmax, Tlast , t1/2, CL/F, Vz/F
Measured: 0, 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12h post dose
Number of Participants with adverse events
Measured: up to 24 hr
Change from baseline in clinical laboratory tests (hematology, chemistry and urinalysis)
Measured: 0, 24h post dose
Change from baseline in vital signs (blood pressure and heart rate)
Measured: 0 ,1 , 2, 3, 4, 5, 6, 24h post dose
Change from baseline in 12-lead ECG
Measured: 0, i, 2, 3, 6, 24h post dose
Profile of urine pharmacokinetics
Ae, CLr, %Fx
Measured: 0-4, 4-10, 10-12, 12-24h post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startSep 2011
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amicus Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Clinical Research, Study director, Amicus Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01853852
- Sponsor's protocol ID
- 115806
- Status last verified
- Dec 2013
- First submitted
- 10 Nov 2011
- Last updated
- 18 Dec 2013
- Results posted
- No
Publications
Ino H, Takahashi N, Terao T, Mudd PN Jr, Hirama T. Pharmacokinetics, safety, and tolerability following single-dose migalastat hydrochloride (GR181413A/AT1001) in healthy male Japanese subjects. J Drug Assess. 2013 Jul 24;2(1):87-93. doi: 10.3109/21556660.2013.827117. eCollection 2013.
PubMed 27536442
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01853852
- Acronym / sponsor ID
- 115806
- Conditions
- Fabry Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Amicus TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 50 mg | Experimental | Drug: GR181413A/AT1001 solution, Other: Potable water, Drug: Placebo capsuleGR181413A/AT1001 |
| 150 mg | Experimental | Drug: GR181413A/AT1001 capsuleGR181413A/AT1001 |
| 450 mg | Experimental | Drug: GR181413A/AT1001 capsuleGR181413A/AT1001 |
| Placebo | Placebo comparator | Drug: GR181413A/AT1001 solution, Drug: GR181413A/AT1001 capsule, Other: Potable water, Drug: Placebo capsuleplacebo |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
- Male or female between 20 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 female.
- 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.
- Body weight >=50 kg and BMI within the range 18.5 - 29.0 kg/m2 (inclusive).
Key exclusion criteria (14 listed)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GR181413A/AT1001 solutionPowder for reconstitution | Drug | 50 mg, Placebo |
| GR181413A/AT1001 capsuleSize 2, hard gelatin capsule, white opaque / blue opaque | Drug | 150 mg, 450 mg, Placebo |
| Potable waterMatched, Size 2, hard gelatin capsule, white opaque/blue opaque | Other | 50 mg, Placebo |
| Placebo capsuleSolution matched | Drug | 50 mg, Placebo |
Primary outcome
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
Number of Participants with adverse events
Time frame: up to 24 hr
Change from baseline in clinical laboratory tests (hematology, chemistry and urinalysis)
Time frame: 0, 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
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
Ae, CLr, %Fx
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
- Derived from this study: PubMed 27536442Ino H, Takahashi N, Terao T, Mudd PN Jr, Hirama T. Pharmacokinetics, safety, and tolerability following single-dose migalastat hydrochloride (GR181413A/AT1001) in healthy male Japanese subjects. J Drug Assess. 2013 Jul 24;2(1):87-93. doi: 10.3109/21556660.2013.827117. eCollection 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor, Clinical Research study director
Amicus Therapeutics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GR181413A/AT1001 solution, GR181413A/AT1001 capsule and Potable water in people with Fabry Disease, run by Amicus Therapeutics at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Profile of plasma pharmacokinetics (time frame: 0, 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12h post dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01853852, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2013.