Fabry DiseasePhase 1NCT01730469
Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function
A Phase 1 study testing AT1001 150 mg in people with Fabry Disease, run by Amicus Therapeutics at 4 sites in United States.
Trial summary
This study will assess the safety, tolerability, and pharmacokinetics (PK) study of a single dose of 150 mg AT1001 (migalastat HCl, GR181413A) administered orally to healthy subjects with normal renal function and to subjects with mild, moderate, and severe renal impairment. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Fabry Disease
- What is being tested?
- AT1001 150 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2011to Apr 2012
- 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- males or females aged 18 to 70 years inclusive (subjects with normal renal function, mild or moderate renal impairment), and 18 to 75 years inclusive (subjects with severe renal impairment)
- body mass index 18.0 to 40.0 kilogram (kg)/square meter (m^2) inclusive
- females who are non-pregnant, non-lactating, or postmenopausal for >=1 year, surgically sterile for >= 90 days, or agree to use approved methods of contraception
- males will be sterile or use approved methods of contraception
- understands and signs informed consent form Healthy subjects with normal renal function
- negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in
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- good health with no clinically significant medical history, physical examination, vital signs, or 12-lead ECG
- clinical laboratory tests within the reference range or not clinically significant
- normal renal function (estimated CLcr >90 mL/min) at Screening Subjects with mild, moderate or severe renal impairment
- negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in or verification of a prescription for a positive test
- renal impairment (estimated CLcr <90 mL/min)
- evidence of stable renal impairment defined as two separate estimated CLcr values within 25%
- clinical laboratory results consistent with their renal condition or of no clinical significance for the study
- abnormal laboratory values must not be clinically significant. Anemia secondary to renal disease is acceptable if hemoglobin is ≥9 g/dL and no clinically significant symptoms. Liver enzymes and bilirubin must be below twice the upper normal level
- subjects with renal impairment must have stable underlying medical conditions < 90 days before study start
- stable medication regimen(s) (no new drug(s) or changed dosage(s) <30 days before study drug)
- in good general health, allowing for concurrent illnesses associated with chronic kidney disease
Who cannot join
- All subjects:
- history of hypersensitivity or allergies to any drug, unless approved by the Investigator and reviewed by Sponsor/Medical Monitor
- participation in a study with receipt of an investigational drug < 5 half-lives or 30 days (whichever is longer) before Check-in
- use of alcohol, grapefruit, or caffeine-containing foods or beverages < 72 hours before Check-in, unless approved by the Investigator and reviewed by the Sponsor/Medical Monitor
- poor peripheral venous access
- whole blood donation < 56 days before dosing or plasma donation < 14 days before dosing
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- receipt of blood products < 2 months before Check-in
- history or presence of any clinically significant abnormal ECG
- history of alcoholism or drug addiction < 1 year before Check-in
- positive test for HIV antibody, HBsAg or anti-HCV
- pregnant or breastfeeding
- Healthy subjects with normal renal function:
- use of any tobacco- or nicotine-containing products < 6 months before Check-in
- clinically significant (history of or active) cardiac, hepatic, pulmonary, endocrine, neurological, infectious, gastrointestinal, hematologic, oncologic, or psychiatric disease putting the subject at increased risk or could interfere with study objectives
- screening laboratory values outside normal range and deemed clinically significant by the Investigator
- use of a prescription drug < 14 days of dosing or a non-prescription drug < 7 days before dosing or need of concomitant medication during the study
- Subjects with mild, moderate, or severe renal impairment:
- unstable disease (concurrent medical conditions that have changed significantly < 90 days)
- changes in concomitant prescription medications < 30 days before dosing or expected changes during study
- use of new non-prescription medication < 30 days before dosing
- renal transplant
- acute or chronic non-renal condition limiting the subject's ability to complete and/or participate in the study
Trial locations and contacts
4 sites in 1 country.
United States4 sites
GSK Investigational Site
Costa Mesa, California, 92626
GSK Investigational Site
Miami, Florida, 33014
GSK Investigational Site
Miami, Florida, 33169
GSK Investigational Site
Orlando, Florida, 32809
About this study
Official title: An Open-Label Study to Determine the Safety and Pharmacokinetics of AT1001 in Subjects With Impaired Renal Function and Healthy Subjects With Normal Renal Function (AT1001-015)
This study will assess the safety, tolerability, and pharmacokinetics (PK) study of a single dose of 150 mg AT1001 (migalastat HCl, GR181413A) administered orally to healthy subjects with normal renal function and to subjects with mild, moderate, and severe renal impairment.
Read the detailed description
This will be an open-label, non-randomized, multiple-center, sequential group, safety, tolerability, and PK study of a single dose of AT1001 (migalastat HCl, GR181413A) administered orally as a 150 mg dose in fasted healthy control male and female subjects with normal renal function compared to mild, moderate, and severe renally-impaired subjects (classified by level of creatinine clearance [CLcr] as determined by the Cockcroft-Gault formula).
Screening will occur from Day -28 to Day -2. Subjects will check-in to the clinic on Day -1 and receive a single oral dose of 150 mg AT1001 on Day 1. Subjects will be discharged from the clinic on Day 2 (if stable as determined by the Investigator) and return for daily visits on Day 3 through Day 6 for a safety assessment and PK sampling. Subjects will undergo a follow-up visit on Day 7 (+1) and an end of study visit on Day 10 (+1).
- Conditions
- Fabry Disease
- Being tested
- AT1001 150 mg
- Keywords
- Pharmacokinetics, GR181413, Safety, AT1001, Migalastat hydrochloride
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT1001 150 mgDrug
Also called migalastat HCl, GR181413A
AT1001 150mg is available as a capsule
| Study group | Role | What they receive |
|---|---|---|
| AT1001 150 mg | Experimental | Each subject will receive a single oral dose of AT1001 150 mg administered orally with 240 mL room temperature water after at least a 4-hour fast Receives: Drug: AT1001 150 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events to assess safety and tolerability
Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).
Measured: Day 1 to Day 10 (+1)
Clinical laboratory test values to assess safety and tolerability
Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.
Measured: Day -28 to Day 10 (+1)
Vital signs to assess safety and tolerability
Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.
Measured: Day -28 to Day 10 (+1)
Physician examination to assess safety and tolerability
Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.
Measured: Day -28 to Day 10 (+1)
Measure of ECG to assess safety and tolerability
Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm. All subjects will undergo ECG testing.
Measured: Day -28 to Day 10 (+1)
Secondary outcomes (8)
Maximum observed concentration (Cmax) of AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the resultant maximum plasma concentration (Cmax) will be measured in subjects with impaired renal function and normal renal function.
Measured: Day 1 to Day 6
Time to achieve maximum concentration (Tmax) of AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and time to maximum concentration (tmax) will be measured in subjects with impaired renal function and normal renal function.
Measured: Day 1 to Day 6
Apparent terminal elimination half life (t1/2 ) of AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and and apparent terminal elimination half-life (t1/2) will be measured in subjects with impaired renal function and normal renal function.
Measured: Day 1 to Day 6
Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-t will be measured in subjects with impaired renal function and normal renal function
Measured: Day 1 to Day 6
Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-inf will be measured in subjects with impaired renal function and normal renal function
Measured: Day 1 to Day 6
Apparent terminal elimination rate constant for AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the apparent terminal elimination rate constant will be measured in subjects with impaired renal function and normal renal function
Measured: Day 1 to Day 6
Oral clearance of AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral clearance will be measured in subjects with impaired renal function and normal renal function
Measured: Day 1 to Day 6
Oral volume of distribution of AT1001
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral volume of distribution will be measured in subjects with impaired renal function and normal renal function
Measured: Day 1 to Day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2012 (estimated)
- Study startAug 2011
- Primary completionApr 2012
- Study completionApr 2012
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 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
- NCT01730469
- Sponsor's protocol ID
- 116431
- Status last verified
- Aug 2017
- First submitted
- 8 Nov 2012
- Last updated
- 3 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Johnson FK, Mudd PN Jr, DiMino T, Vosk J, Sitaraman S, Boudes P, France N, Barlow C. An open-label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function. Clin Pharmacol Drug Dev. 2015 Jul;4(4):256-61. doi: 10.1002/cpdd.149. Epub 2014 Dec 22.
PubMed 27136905
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Determine the Safety and Pharmacokinetics of AT1001 in Subjects With Impaired Renal Function and Healthy Subjects With Normal Renal Function (AT1001-015)
- ClinicalTrials.gov ID
- NCT01730469
- Acronym / sponsor ID
- 116431
- Conditions
- Fabry Disease
- Keywords
- Pharmacokinetics, GR181413, Safety, AT1001, Migalastat hydrochloride
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Amicus TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 21 Nov 2012 (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.
This study will assess the safety, tolerability, and pharmacokinetics (PK) study of a single dose of 150 mg AT1001 (migalastat HCl, GR181413A) administered orally to healthy subjects with normal renal function and to subjects with mild, moderate, and severe renal impairment.
Detailed description
This will be an open-label, non-randomized, multiple-center, sequential group, safety, tolerability, and PK study of a single dose of AT1001 (migalastat HCl, GR181413A) administered orally as a 150 mg dose in fasted healthy control male and female subjects with normal renal function compared to mild, moderate, and severe renally-impaired subjects (classified by level of creatinine clearance [CLcr] as determined by the Cockcroft-Gault formula).
Screening will occur from Day -28 to Day -2. Subjects will check-in to the clinic on Day -1 and receive a single oral dose of 150 mg AT1001 on Day 1. Subjects will be discharged from the clinic on Day 2 (if stable as determined by the Investigator) and return for daily visits on Day 3 through Day 6 for a safety assessment and PK sampling. Subjects will undergo a follow-up visit on Day 7 (+1) and an end of study visit on Day 10 (+1).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AT1001 150 mg | Experimental | Drug: AT1001 150 mgEach subject will receive a single oral dose of AT1001 150 mg administered orally with 240 mL room temperature water after at least a 4-hour fast |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- males or females aged 18 to 70 years inclusive (subjects with normal renal function, mild or moderate renal impairment), and 18 to 75 years inclusive (subjects with severe renal impairment)
- body mass index 18.0 to 40.0 kilogram (kg)/square meter (m^2) inclusive
- females who are non-pregnant, non-lactating, or postmenopausal for >=1 year, surgically sterile for >= 90 days, or agree to use approved methods of contraception
- males will be sterile or use approved methods of contraception
- understands and signs informed consent form Healthy subjects with normal renal function
Key exclusion criteria (22 listed)
- history of hypersensitivity or allergies to any drug, unless approved by the Investigator and reviewed by Sponsor/Medical Monitor
- participation in a study with receipt of an investigational drug < 5 half-lives or 30 days (whichever is longer) before Check-in
- use of alcohol, grapefruit, or caffeine-containing foods or beverages < 72 hours before Check-in, unless approved by the Investigator and reviewed by the Sponsor/Medical Monitor
- poor peripheral venous access
- whole blood donation < 56 days before dosing or plasma donation < 14 days before dosing
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 |
|---|---|---|
| AT1001 150 mgAlso: migalastat HCl, GR181413AAT1001 150mg is available as a capsule | Drug | AT1001 150 mg |
Primary outcome
Number of subjects with adverse events to assess safety and tolerability
Time frame: Day 1 to Day 10 (+1)
Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).
Clinical laboratory test values to assess safety and tolerability
Time frame: Day -28 to Day 10 (+1)
Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.
Vital signs to assess safety and tolerability
Time frame: Day -28 to Day 10 (+1)
Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.
Physician examination to assess safety and tolerability
Time frame: Day -28 to Day 10 (+1)
Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.
Measure of ECG to assess safety and tolerability
Time frame: Day -28 to Day 10 (+1)
Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm. All subjects will undergo ECG testing.
8 secondary outcomes
Maximum observed concentration (Cmax) of AT1001
Time frame: Day 1 to Day 6
Time to achieve maximum concentration (Tmax) of AT1001
Time frame: Day 1 to Day 6
Apparent terminal elimination half life (t1/2 ) of AT1001
Time frame: Day 1 to Day 6
Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001
Time frame: Day 1 to Day 6
Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
Time frame: Day 1 to Day 6
Apparent terminal elimination rate constant for AT1001
Time frame: Day 1 to Day 6
Oral clearance of AT1001
Time frame: Day 1 to Day 6
Oral volume of distribution of AT1001
Time frame: Day 1 to Day 6
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 3 Aug 2017.
- Derived from this study: PubMed 27136905Johnson FK, Mudd PN Jr, DiMino T, Vosk J, Sitaraman S, Boudes P, France N, Barlow C. An open-label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function. Clin Pharmacol Drug Dev. 2015 Jul;4(4):256-61. doi: 10.1002/cpdd.149. Epub 2014 Dec 22.
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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
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AT1001 150 mg in people with Fabry Disease, run by Amicus Therapeutics at 4 sites in United States.
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 17 inclusion and 22 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 3 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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. 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?
Number of subjects with adverse events to assess safety and tolerability (time frame: Day 1 to Day 10 (+1)). The study lists 5 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 NCT01730469, 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 3 Aug 2017.