Fabry DiseasePhase 1NCT01730482
A Study to Assess the Absorption, Metabolism and Excretion of Migalastat Hydrochloride (AT1001-014)
A Phase 1 study testing [14C] AT1001 in people with Fabry Disease, run by Amicus Therapeutics.
Trial summary
This study is designed to describe the metabolism of AT1001 (migalastat HCl) and the contribution of metabolism and urinary excretion to its overall elimination as part of the continuing assessment of the safety and effectiveness of the drug. Read more about this study
- Who is it for?
- Ages 30 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Fabry Disease
- What is being tested?
- [14C] AT1001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- No sites listed yet
- Study dates
- Aug 2011to Sep 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 30 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male subjects between the ages of 30 and 55 years, inclusive
- Body mass index (BMI) of >=18.0 to <=30.0 and weighing at least 60 kg
- Anticipated, regular, average bowel movements of 1-2 per day
- No clinically significant abnormal findings on the physical exam, vital signs, serum chemistry, hematology, and urinalysis values, as deemed by the principal investigator
- Willing to avoid taking of all over-the-counter medications 7 days and all prescription drugs 14 days prior to Day -1
- Willing to abstain from sexual intercourse or employ a barrier method of contraception during the inpatient clinic confinement and until the follow-up visit
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- Willing to avoid ingestion of broccoli, brussels sprouts, grapefruit, grapefruit juice, or charbroiled meat during the period of confinement in the clinical unit
- Willingness to consume a fiber-rich diet during the period of confinement in the clinic
- Willingness to avoid vigorous physical activity during inpatient clinic confinement and through the follow-up visit
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, other study procedures, and study restrictions
- Provide written informed consent to participate in the study
Who cannot join
- Any previous or ongoing clinically significant illness, medical condition, medical history, physical findings, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject, or alter the absorption, distribution, metabolism, or excretion of the study drug, or could impair the assessment of study results
- History or presence of significant ophthalmic, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease
- History of a major surgical procedure within 30 days before screening
- History of blood or plasma donation or blood loss (>400 mL) within 60 days before screening
- History of drug or alcohol abuse or addiction within 2 years before screening
- Intake of more than 2 alcoholic drinks per day within the past 7 days or use of alcohol-, grapefruit-, or caffeine-containing foods or beverages within 72 hours prior to Day -1
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- Self-reported smoker (occasional or frequent) or positive urine cotinine test (measured at screening and baseline) exceeding the local laboratory's lower limit of detection.
- Presence or history of severe adverse reaction to any drug; history of hypersensitivity or allergic reaction to AT1001 or related iminosugars
- Receipt of any investigational agent or participation in any other interventional clinical trial within the past 30 days
- Participation in any clinical study involving administration of [14C] labeled compound(s) within the last 12 months. A subject's previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study
- At Day -1, a drug toxicology screen positive for any illicit substances, or alcohol
- Anticipated need for alcohol, tobacco, or any drug during the period of confinement in the clinical unit
About this study
Official title: A Phase 1 Study to Investigate the Absorption, Metabolism and Excretion of [14C] AT1001 (Migalastat Hydrochloride) Following a Single Oral Administration in Healthy Volunteers (AT1001-014)
This study is designed to describe the metabolism of AT1001 (migalastat HCl) and the contribution of metabolism and urinary excretion to its overall elimination as part of the continuing assessment of the safety and effectiveness of the drug.
This is a Phase 1, single-site, open-label, single dose study of the absorption, metabolism and excretion of radiolabeled AT1001 in healthy male subjects between 30 and 55 years of age, inclusive. Six subjects will be dosed, with the goal of having at least 4 subjects complete the study through follow-up. All subjects will be screened within 28 days before admission to the Clinical Unit. Subjects will be confined to the clinical unit for 10 days after dosing and will return to the clinic for a follow-up visit 28 days after dosing.
Each subject will receive a single oral dose of AT1001 as an aqueous solution containing 150 mg [14C] AT1001 (1 μCi). Blood, duodenal bile, expired air, urine, and feces samples will be collected at specified time points after dosing throughout the period of confinement at the study site. Safety will be assessed throughout the study by monitoring clinical laboratory tests, ECGs, physical examinations, vital signs, and adverse events. The total duration of the study for each subject is approximately 8 weeks.
- Conditions
- Fabry Disease
- Being tested
- [14C] AT1001
- Keywords
- excretion, healthy volunteer, migalastat hydrochloride, AT1001, pharmacokinetics, Fabry disease
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[14C] AT1001Drug
150 mg of [14C] labelled AT1001 will be administered as a solution (prepared by weighing 150 mg of AT1001 powder and dissolving in 100 mL of water). The entire solution will be swallowed orally. After ingestion of study medication, the dosing bottle will be rinsed with 50 mL of water and this will be ingested by the subject. This rinse procedure should be performed twice. Following the second rinse ingestion, the subjects should be instructed to drink additional water to bring the total volume ingested to 240 mL.
| Study group | Role | What they receive |
|---|---|---|
| [14C] AT1001 Arm | Experimental | Each subject will receive a single oral dose of 150 mg of [14C] AT1001 as an aqueous solution containing 1 μCi AT1001 on Study Day 1. Receives: Drug: [14C] AT1001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recovery of total radioactivity in urine
Urine will be collected: pre-dose (-12-0 hours), 0-12 and 12-24 hours on Day 1, 24-hourly on Days 2-10; the last sample will be collected on Day 11. Total radioactivity excreted in urine will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in urine, divided by the duration of collection. The percentage of dose excreted in urine will be calculated from the total amount excreted in urine divided by the dose administered, multiplied by 100.
Measured: Days 1 to 11
Recovery of total radioactivity in feces
Feces will be collected: predose (-24 to 0 hours); all bowel movements post-dose will be collected on Days 1 to 10; the last sample will be collected on Day 11. Total radioactivity excreted in feces will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in feces, divided by the duration of collection. The percentage of dose excreted in feces will be calculated from the total amount excreted in feces divided by the dose administered, multiplied by 100.
Measured: Days 1 to 11
Presence of radioactivity in expired air
Expired air will be collected: pre-dose and at 2, 4, 6 and 24 hours after dosing. Each subject will blow into a measured volume of sodium hydroxide solution containing phenolphthalein, until an indicator changes color, showing that the sodium hydroxide is saturated. This sodium hydroxide solution will be analysed for radioactive content. If radioactivity is detected the total amount in expired air during the collection period will be calculated.
Measured: Day 1
Plasma AT1001 pharmacokinetic parameters
Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma AT1001: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.
Measured: Days 1 to 10
Plasma total radioactivity pharmacokinetic parameters
Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma radioactivity: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.
Measured: Days 1 to 10
Secondary outcomes (7)
Number of subjects with adverse events as a measure of safety and tolerability
Adverse events (AEs) will be collected from the start of Investigation Product and until the follow-up visit.
Measured: Day 1 to Day 29
Measure of clinical laboratory test values to access safety and tolerability
Clinical laboratory tests will include hematology, coagulation tests, clinical chemistry, urinalysis, drug and toxicology screen, Hepatitis A and HIV screen.
Measured: Upto 8 weeks
Physical examination to access safety and tolerability
Physical examination results will be categorized as normal, abnormal clinically significant, or abnormal not clinically significant
Measured: Upto 8 weeks
Measure of vital signs to access safety and tolerability
Vital sign measurements will include pulse, respiratory rate, blood pressure, and oral temperature). Subjects should be in a supine position for at least 5 minutes prior to taking measurements.
Measured: Upto 8 weeks
Measure of ECG to access safety and tolerability
Electrocardiograph (ECG) is a machine that measures the electrical activity of the heart and records changes in the hearts' rhythm. All subjects will undergo ECG testing.
Measured: Upto 8 weeks
The blood to plasma ratio of total radioactivity
The ratio of plasma to blood radioactivity will be calculated at 2, 4, 6 and 24 hours after administration of AT1001.
Measured: Day 1
Characterization of metabolites in plasma, urine, duodenal bile and fecal homogenates
An Entero-Test capsule will be ingested to collect duodenal bile and will be removed after sample collection. Metabolite elucidation and identification will be performed in the collected plasma, urine doudenal bile, and fecal samples, if feasible, under a separate study. Results will be summarized in a separate report.
Measured: Day -1 to Day 11
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 completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 6 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
- NCT01730482
- Sponsor's protocol ID
- 116435
- Status last verified
- Dec 2013
- First submitted
- 8 Nov 2012
- Last updated
- 18 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
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 1 Study to Investigate the Absorption, Metabolism and Excretion of [14C] AT1001 (Migalastat Hydrochloride) Following a Single Oral Administration in Healthy Volunteers (AT1001-014)
- ClinicalTrials.gov ID
- NCT01730482
- Acronym / sponsor ID
- 116435
- Conditions
- Fabry Disease
- Keywords
- excretion, healthy volunteer, migalastat hydrochloride, AT1001, pharmacokinetics, Fabry disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Amicus TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (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 is designed to describe the metabolism of AT1001 (migalastat HCl) and the contribution of metabolism and urinary excretion to its overall elimination as part of the continuing assessment of the safety and effectiveness of the drug.
This is a Phase 1, single-site, open-label, single dose study of the absorption, metabolism and excretion of radiolabeled AT1001 in healthy male subjects between 30 and 55 years of age, inclusive. Six subjects will be dosed, with the goal of having at least 4 subjects complete the study through follow-up. All subjects will be screened within 28 days before admission to the Clinical Unit. Subjects will be confined to the clinical unit for 10 days after dosing and will return to the clinic for a follow-up visit 28 days after dosing.
Each subject will receive a single oral dose of AT1001 as an aqueous solution containing 150 mg [14C] AT1001 (1 μCi). Blood, duodenal bile, expired air, urine, and feces samples will be collected at specified time points after dosing throughout the period of confinement at the study site. Safety will be assessed throughout the study by monitoring clinical laboratory tests, ECGs, physical examinations, vital signs, and adverse events. The total duration of the study for each subject is approximately 8 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [14C] AT1001 Arm | Experimental | Drug: [14C] AT1001Each subject will receive a single oral dose of 150 mg of [14C] AT1001 as an aqueous solution containing 1 μCi AT1001 on Study Day 1. |
Who may qualify
- Ages
- 30 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy male subjects between the ages of 30 and 55 years, inclusive
- Body mass index (BMI) of >=18.0 to <=30.0 and weighing at least 60 kg
- Anticipated, regular, average bowel movements of 1-2 per day
- No clinically significant abnormal findings on the physical exam, vital signs, serum chemistry, hematology, and urinalysis values, as deemed by the principal investigator
- Willing to avoid taking of all over-the-counter medications 7 days and all prescription drugs 14 days prior to Day -1
Key exclusion criteria (12 listed)
- Any previous or ongoing clinically significant illness, medical condition, medical history, physical findings, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject, or alter the absorption, distribution, metabolism, or excretion of the study drug, or could impair the assessment of study results
- History or presence of significant ophthalmic, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease
- History of a major surgical procedure within 30 days before screening
- History of blood or plasma donation or blood loss (>400 mL) within 60 days before screening
- History of drug or alcohol abuse or addiction within 2 years before screening
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 |
|---|---|---|
| [14C] AT1001150 mg of [14C] labelled AT1001 will be administered as a solution (prepared by weighing 150 mg of AT1001 powder and dissolving in 100 mL of water). The entire solution will be swallowed orally. After ingestion of study medication, the dosing bottle will be rinsed with 50 mL of water and this will be ingested by the subject. This rinse procedure should be performed twice. Following the second rinse ingestion, the subjects should be instructed to drink additional water to bring the total volume ingested to 240 mL. | Drug | [14C] AT1001 Arm |
Primary outcome
Recovery of total radioactivity in urine
Time frame: Days 1 to 11
Urine will be collected: pre-dose (-12-0 hours), 0-12 and 12-24 hours on Day 1, 24-hourly on Days 2-10; the last sample will be collected on Day 11. Total radioactivity excreted in urine will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in urine, divided by the duration of collection. The percentage of dose excreted in urine will be calculated from the total amount excreted in urine divided by the dose administered, multiplied by 100.
Recovery of total radioactivity in feces
Time frame: Days 1 to 11
Feces will be collected: predose (-24 to 0 hours); all bowel movements post-dose will be collected on Days 1 to 10; the last sample will be collected on Day 11. Total radioactivity excreted in feces will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in feces, divided by the duration of collection. The percentage of dose excreted in feces will be calculated from the total amount excreted in feces divided by the dose administered, multiplied by 100.
Presence of radioactivity in expired air
Time frame: Day 1
Expired air will be collected: pre-dose and at 2, 4, 6 and 24 hours after dosing. Each subject will blow into a measured volume of sodium hydroxide solution containing phenolphthalein, until an indicator changes color, showing that the sodium hydroxide is saturated. This sodium hydroxide solution will be analysed for radioactive content. If radioactivity is detected the total amount in expired air during the collection period will be calculated.
Plasma AT1001 pharmacokinetic parameters
Time frame: Days 1 to 10
Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma AT1001: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.
Plasma total radioactivity pharmacokinetic parameters
Time frame: Days 1 to 10
Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma radioactivity: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.
7 secondary outcomes
Number of subjects with adverse events as a measure of safety and tolerability
Time frame: Day 1 to Day 29
Measure of clinical laboratory test values to access safety and tolerability
Time frame: Upto 8 weeks
Physical examination to access safety and tolerability
Time frame: Upto 8 weeks
Measure of vital signs to access safety and tolerability
Time frame: Upto 8 weeks
Measure of ECG to access safety and tolerability
Time frame: Upto 8 weeks
The blood to plasma ratio of total radioactivity
Time frame: Day 1
Characterization of metabolites in plasma, urine, duodenal bile and fecal homogenates
Time frame: Day -1 to Day 11
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.
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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
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [14C] AT1001 in people with Fabry Disease, run by Amicus Therapeutics.
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 11 inclusion and 12 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.
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?
Recovery of total radioactivity in urine (time frame: Days 1 to 11). 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?
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.