A Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Debio 1450 in Healthy Subjects

Healthy Participants Clinical Trial

Official title:

A Phase 1, Open-Label, Fixed Sequence Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Debio 1450 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03209648
• Other study ID #: Debio 1450-111
• Secondary ID: 2017-001352-60
• Status: Completed
• Phase: Phase 1
• First received: July 4, 2017
• Last updated: October 17, 2017
• Start date: June 14, 2017
• Est. completion date: August 31, 2017

Study information

• Verified date: October 2017
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Debio 1450 is metabolised mainly by CYP3A4, therefore inhibitors of CYP3A4 have the potential to raise Debio 1450 plasma concentrations. Hence, it is important to determine the effect of CYP3A4 inhibition by itraconazole on the Pharmacokinetics of Debio 1450.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 31, 2017
• Est. primary completion date: August 23, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Meets protocol-specified criteria for qualification and contraception.

• Is willing and able to comply with restrictions related to food, drink and medications.

• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures.

Exclusion Criteria:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters.

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

• the safety or well-being of the participant or study staff.

• the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding); the analysis of results.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Debio 1450
Debio 1450, 40 mg capsule.
• Itraconazole
Itraconazole, 20 mL of 10 mg/mL solution.

Locations

Country	Name	City	State
United Kingdom	Covance Clinical Research Unit Ltd.	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Debio 1452		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Primary	Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC0-8) of Debio 1452		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Primary	Area Under the Plasma Concentration-time Curve from Time Zero to Time (t) (AUC0-t) of Debio 1452		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Area Under the Plasma Concentration-time Curve from Time Zero to 12 Hours Postdose (AUC0-12) of Debio 1452, Debio 1450, Debio 1452-M1, and desmethyl Debio 1452		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Time to Reach Maximum Concentration (Tmax) of Debio 1452, Debio 1450, Debio 1452-M1, desmethyl Debio 1452 and Itraconazole		Debio 1450 and its metabolites: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose. Itraconazole: Days 1, 3, and 6: predose, Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Secondary	Apparent Plasma Terminal Elimination Half-life (t1/2) of Debio 1452, Debio 1450, Debio 1452-M1, desmethyl Debio 1452 and Itraconazole		Debio 1450 and its metabolites: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose. Itraconazole: Days 1, 3, and 6: predose, Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Secondary	Mean Residence Time (MRT) of Debio 1452, Debio 1450, Debio 1452-M1, and desmethyl Debio 1452	the mean residence time is the average time the drug stays at the site of action.	Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Apparent Total Body Clearance of a Drug from the Plasma (CL/F) of Debio 1452	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Apparent Volume of Distribution During the Terminal (lamdaz) Phase (Vz/F) of Debio 1452	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.	Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Maximum Observed Plasma Concentration (Cmax) of Debio 1450, Debio 1452-M1, desmethyl Debio 1452 and Itraconazole		Debio 1450 and its metabolites: Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose. Itraconazole: Days 1, 3, and 6: predose, Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Secondary	Area Under the Plasma Concentration-time Curve from Time Zero to Time (t) (AUC0-t) of Debio 1450, Debio 1452-M1 and desmethyl Debio 1452		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC0-infinity) of Debio 1450, Debio 1452-M1 and desmethyl Debio 1452		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Metabolite:Parent Cmax Ratio (for Debio 1452-M1 and desmethyl Debio 1452 only; Debio 1452 as Parent; Based on Molar Data)		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Metabolite:Parent AUC ratio (for Debio 1452-M1 and desmethyl Debio 1452 only; Debio 1452 as Parent; Based on Molar Data)		Days 1 and 5: predose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 30, 36, 48, and 60 hours postdose
Secondary	Area Under the Plasma Concentration-time Curve During a Dosing Interval at Steady State (AUC0-t) of Itraconazole		Days 1, 3, and 6: predose Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Secondary	Measured Concentration at the end of a Dosing Interval at Steady State (Ctrough) of Itraconazole		Days 1, 3, and 6: predose Days 4 and 5: predose, and 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Secondary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	Baseline up to Week 7