Bioavailability of Levoketoconazole and Ketoconazole Tablets

A Phase 1 Randomized, Open-Label, Two-Period,Two-Sequence Crossover Study to Evaluate the Relative Oral Bioavailability of Levoketoconazole and Ketoconazole Tablets in Healthy Subjects

This is a phase 1, randomized, open-label, single-dose, two-period, two-sequence crossover study in healthy male and female subjects to evaluate the relative oral bioavailability of levoketoconazole tablets (the test drug) and ketoconazole tablets (the reference drug product).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Levoketoconazole; Drug: Ketoconazole

Detailed Description

This is a phase 1, randomized, open-label, single-dose, two-period, two-sequence crossover study in healthy male and female subjects to evaluate the relative oral bioavailability of levoketoconazole tablets (the test drug) and ketoconazole tablets (the reference drug product). Subjects will be randomized to receive a single oral dose of 150 mg levoketoconazole (Study Drug A) or a single oral dose of 200 mg ketoconazole (Study Drug B) in each period.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Pharmaceutical Research Associates, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to 55 years of age, inclusive, at time of consent.
2. Body mass index (BMI) between 18.0 and 32.0 kg/m2,inclusive.
3. In good general physical health as determined by absence of clinically significant medical history, physical examination findings, vital signs, clinical laboratory evaluations, and ECG measurements.
4. Has not consumed and agrees to abstain from taking any prescription drugs, dietary supplements including vitamins and herbal preparations, or non-prescription drugs for 14 days prior to clinical research unit (CRU) admission, during washout period, and through Follow-Up.
5. Has not consumed alcohol-containing beverages for 3 days prior to CRU admission and agrees not to consume alcohol through Follow-Up.
6. Is a nonsmoker (for at least 3 months) with negative urinary cotinine test at Screening and agrees to abstain from tobacco-and nicotine-containing products for the duration of the study.

Exclusion Criteria:

1. Evidence of any out-of-normal-range laboratory value at Screening that has not been reviewed, approved, and documented as Not Clinically Significant by the Investigator.
2. Concurrent medical illness that would interfere with the conduct of the study in the opinion of the Investigator.
3. History or presence of clinically significant cardiovascular, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, psychiatric, renal, hepatic, chronic respiratory, or gastrointestinal disease as judged by the Investigator.
4. Positive urine drug screen for drugs-of-abuse, including cocaine, tetrahydrocannabinol, opioids, benzodiazepines, amphetamines, and barbiturates,and/or positive urine screen for alcohol at Screening and CRU admission.
5. Treatment with an investigational drug within the longer of 30 days or five half-lives of the investigational drug preceding the first dose of study drug.
6. Positive for HIV, hepatitis B, and/or hepatitis C on Screening assessments.
7. Acute illness within 7 days of CRU admission.
8. Donated plasma within 7 days of drug administration.
9. Donated 1 or more pints of blood (or equivalent blood loss) within 30 days prior to drug administration.
10. History of caffeine consumption exceeding 8 cups coffee/day within 14 days prior to first dose, or consumption of any caffeine-or chocolate-containing products for 3 days prior to CRU admission each week.
11. Female subjects who are pregnant or lactating.
12. Males with hemoglobin less than 12.0 g/dL at Screening or CRU admission; Females with hemoglobin less than 11.0 g/dL at Screening or CRU admission
13. Had difficulties with swallowing whole tablets.
14. Body habitus preventing repeated venipuncture as required by protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Levoketoconazole; Levoketoconazole 150 mg	Drug: Levoketoconazole; Levoketoconazole tablet; Other Names: COR-003
ACTIVE_COMPARATOR: Ketoconazole; Ketoconazole 200 mg	Drug: Ketoconazole; Ketoconazole tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of geometric least squares means for AUClast of plasma levoketoconazole (2S,4R-ketoconazole)	Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)	24 hours
Ratio of geometric least squares means for AUCinf of plasma levoketoconazole (2S,4R-ketoconazole)	Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)	24 hours
Ratio of geometric least squares means for Cmax of plasma levoketoconazole (2S,4R-ketoconazole)	Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Terminal phase rate constant (λz)	Single-dose plasma PK parameters after a single administration of levoketoconazole and ketoconazole in the fasted state including λz	24 hours
Time to Maximum Plasma concentration (Tmax)	Single-dose plasma PK parameters after a single administration of levoketoconazole and ketoconazole in the fasted state including Tmax	24 hours
Lag-time (Tlag)	Single-dose plasma PK parameters after a single administration of levoketoconazole and ketoconazole in the fasted state including: Tlag	24 hours
Apparent systemic clearance (CL/F)	Single-dose plasma PK parameters after a single administration of levoketoconazole and ketoconazole in the fasted state including: CL/F	24 hours
The percentage of area under the plasma concentration-time curve extrapolated from time 0 to infinity as a percentage of total AUC (%AUCext)	Single-dose plasma PK parameters after a single administration of levoketoconazole and ketoconazole in the fasted state including: %AUCext	24 hours
Volume of Distribution (Vz/F)	Single-dose plasma PK parameters after a single administration of levoketoconazole and ketoconazole in the fasted state including: Vz/F	24 hours
Elimination half-life (T1/2)	Single-dose plasma PK parameters after a single administration of levoketoconazole and ketoconazole in the fasted state including: t½	24 hours
Incidence of adverse events (AEs)	Incidence of Treatment-Emergent AEs (TEAEs), AEs of special interest, and Serious Adverse Events (SAEs)	35 days

Collaborators and Investigators

• Sponsor: Cortendo AB

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 16, 2019
• Primary Completion (ACTUAL): January 18, 2020
• Study Completion (ACTUAL): January 23, 2020

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: December 24, 2019
• First Posted (ACTUAL): December 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole
• Other Study ID Numbers: LKC101A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No