A Study to Assess the Safety, Tolerability and Pharmacokinetics of Lucerastat (CDP923) After Multiple Dosing in Healthy Subjects

Healthy Subjects Clinical Trial

Official title:

A Randomised Double-blind, Placebo-controlled, Ascending Multiple Dose Phase 1 Study of CDP923 in Healthy Volunteers to Assess Safety, Tolerability, Pharmacokinetics and Food Effect

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02944474
• Other study ID #: CDP923-002
• Status: Completed
• Phase: Phase 1
• First received: October 24, 2016
• Last updated: October 25, 2016
• Start date: December 2003
• Est. completion date: May 2004

Study information

• Verified date: October 2016
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 2004
• Est. primary completion date: May 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Signed informed consent form.

• Male subjects aged from 18 to 45 years at screening.

• Body weight between 50 and 100 kg and body mass index (BMI) between 18.0 and 29.0 kg/m2 at screening.

• Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests.

Exclusion Criteria:

• History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study treatments.

• Serious adverse reaction or hypersensitivity to any drug.

• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Lucerastat
Capsule for oral administration containing lucerastat
• Placebo
Placebo capsules matching lucerastat capsules

Locations

Country	Name	City	State
United Kingdom	Investigator Site	Edinburgh

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	Number of participants with adverse events (AEs)	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)	Yes
Primary	Change from baseline in haematology after multiple doses of lucerastat		Up to Day 9	Yes
Primary	Change from baseline in clinical chemistry after mutliple doses of lucerastat		Up to Day 9	Yes
Primary	Change from baseline in heart rate after mutliple doses of lucerastat		Up to Day 9	Yes
Secondary	Change from baseline in haematology after a single dose of lucerastat		At 24 hours post dose	Yes
Secondary	Change from baseline in clinical chemistry after a single dose of lucerastat		At 24 hours post dose	Yes
Secondary	Change from baseline in heart rate after a single dose of lucerastat		At 24 hours post dose	Yes
Secondary	Change from baseline in blood pressure after a single dose of lucerastat		Up to 24 hours post dose	Yes
Secondary	Change from baseline in electrocardiogram (ECG) variables after a single dose of lucerastat		Up to 24 hours post dose	Yes
Secondary	Stool frequency after multiple doses of lucerastat		Every day up to Day 9	Yes
Secondary	Change from baseline in body weight after multiple doses of lucerastat		At Day 9	Yes