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The objectives of this study were to evaluate the safety and tolerability of lucerastat and to determine its pharmacokinetic profile after multiple dosing. Also, the potential effect of food on the pharmacokinetics of lucerastat was explored following a single dose of 500 mg.
The subjects were to be enrolled sequentially to three dose groups, starting with the lowest dose level. Subjects could participate in only one Group. Progression to an increased dose of lucerastat was permitted only after review of all data from the previous cohort suggested that it was safe to do so.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (200 mg) | Experimental | Six subjects received 200 mg of lucerastat twice daily for 7 consecutive days in fasting conditions |
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| Cohort 2 (500 mg) | Experimental | Six subjects received 500 mg of lucerastat as a single dose in the morning of Day 1 in fed conditions. After a 5-day washout, they received the same dose twice daily for 7 consecutive days in fasting conditions |
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| Cohort 3 (500 mg) | Experimental | Six subjects received 500 mg of lucerastat twice daily for 7 consecutive days in fasting conditions |
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| Cohort 4 (1000 mg) | Experimental | Six subjects received 1 g of lucerastat for 7 consecutive days in fasting conditions |
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| Placebo cohorts 1 to 4 | Placebo Comparator | Twelve subjects received matched placebo (3 subjects per cohort, except for Cohort 3 where 4 subjects received placebo) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lucerastat | Drug | Capsule for oral administration containing lucerastat |
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| Measure | Description | Time Frame |
|---|---|---|
| Dose proportionality in lucerastat pharmacokinetics assessed by maximum plasma concentration (Cmax) | Cmax was used to assess dose proportionality across all dose groups | PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose |
| Dose proportionality in lucerastat pharmacokinetics assessed by area under the concentration-time curve (AUC) | AUC from time zero to infinity [AUC(0-inf)] was used to assess dose proportionality across all dose groups | PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose on Day 7 |
| Terminal elimination half-life (t1/2) | t1/2 was calculated from the plasma concentrations-time curves of lucerastat after multiple doses | PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose on Day 7 |
| Food effect on lucerastat pharmacokinetics assessed by Cmax | Potential food effect on pharmacokinetic parameters of lucerastat was tested by comparing Cmax in fed vs fasted state in the 500 mg cohort (cohort 2) | PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose |
| Food effect on lucerastat pharmacokinetics assessed by AUC | Potential food effect on pharmacokinetic parameters of lucerastat was tested by comparing AUC in fed versus fasted state in the 500 mg cohort (cohort 2) | PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose |
| Number of participants with adverse events (AEs) |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in haematology after a single dose of lucerastat | At 24 hours post dose | |
| Change from baseline in clinical chemistry after a single dose of lucerastat | At 24 hours post dose | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Idorsia Pharmaceuticals Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site | Edinburgh | EH14 4AP | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28088251 | Derived | Guerard N, Morand O, Dingemanse J. Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects. Orphanet J Rare Dis. 2017 Jan 14;12(1):9. doi: 10.1186/s13023-017-0565-9. |
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| ID | Term |
|---|---|
| C090092 | migalastat |
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| Placebo | Drug | Placebo capsules matching lucerastat capsules |
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An AE was defined as any untoward medical occurrence in a clinical investigation subject, which did not necessarily have a causal relationship with the treatment |
| From baseline up to Day 14 (end of study) |
| Change from baseline in haematology after multiple doses of lucerastat | Up to Day 9 |
| Change from baseline in clinical chemistry after multiple doses of lucerastat | Up to Day 9 |
| Change from baseline in heart rate after multiple doses of lucerastat | Up to Day 9 |
| Change from baseline in heart rate after a single dose of lucerastat |
| At 24 hours post dose |
| Change from baseline in blood pressure after a single dose of lucerastat | Up to 24 hours post dose |
| Change from baseline in electrocardiogram (ECG) variables after a single dose of lucerastat | Up to 24 hours post dose |
| Stool frequency after multiple doses of lucerastat | Every day up to Day 9 |
| Change from baseline in body weight after multiple doses of lucerastat | At Day 9 |