Drug Interaction Study of Levoketoconazole and Metformin

A Phase I Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Study to Evaluate the Effect of Levoketoconazole on the Single-Dose Pharmacokinetics of Metformin in Healthy Subjects

This is a phase I, open-label, fixed-sequence drug-drug interaction study to evaluate the effect of levoketoconazole on the single-dose PK of metformin in health subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Metformin 500 mg Oral Tablet; Drug: Levoketoconazole 150 - 600 mg (BID)

Detailed Description

This study will enroll healthy male and female subjects to evaluate the effect of levoketoconazole on the PK of a single 500 mg dose of metformin. There will be 3 sequential treatment periods, and all subjects will receive metformin only in Period 1, escalating doses of levoketoconazole in Period 2, and concurrent administration of metformin and levoketoconazole in Period 3.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, LLC

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. 18-55 years of age, inclusive, at time of consent.
2. Body mass index (BMI) between 18 and 32 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 (except as authorized by the Investigator AND Medical Monitor) for 14 days prior to initial CRU admission on Day -1 and through Follow-Up.
5. Has not consumed alcohol-containing beverages for 3 days prior to initial CRU admission on Day -1 and agrees not to consume alcohol for the duration of the study 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 (except for LFTs, which must be within the normal range).
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. Clinically significant ECG abnormality or confirmed QTcF interval > 450 msec at Screening or unconfirmed QTcF interval > 450 msec at CRU admission.
5. Family history (parents, siblings, and offspring) of QT interval sudden cardiac death.
6. Positive urine drug screen for drugs-of-abuse, including cocaine, 3,4 methylenedioxy-methamphetamine (MDMA), tetrahydrocannabinol, opioids, benzodiazepines, amphetamines, and barbiturates, and/or positive urine screen for alcohol at Screening and CRU admission.
7. Positive urinary cotinine test at Screening.
8. 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.
9. Positive for Human Immunodeficiency Virus (HIV), hepatitis B, and/or hepatitis C on Screening assessments.
10. Acute illness within 7 days of the first CRU admission on Day -1.
11. Donated plasma within 7 days of Screening.
12. Donated 1 or more pints of blood (or equivalent blood loss) within 30 days prior to Screening.
13. History of caffeine consumption exceeding 8 cups of coffee/day (1 cup = 8 fluid ounces) 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. Caffeine containing foods and/or beverages (e.g., tea and cola) should be considered equivalent to coffee.
14. History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of hard liquor) within 180 days of Screening.
15. Female subject who is pregnant or lactating.
16. Male with hemoglobin less than 12.0 g/dL; Female with hemoglobin less than 11.0 g/dL.
17. Had difficulties swallowing whole tablets.
18. Body habitus prevents repeated venipuncture.
19. History of hypersensitivity or allergy to metformin.
20. History of hypoglycemia.
21. Participated in the COR-2017-02 levoketoconazole food effect study.
22. History of drug-induced liver injury from any drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Metformin Only	Drug: Metformin 500 mg Oral Tablet; single dose
OTHER: Levoketoconazole Only	Drug: Levoketoconazole 150 - 600 mg (BID); escalating dose from 150 mg to 600 mg (BID); Other Names: COR-003
OTHER: Levoketoconazole + Metformin	Drug: Metformin 500 mg Oral Tablet; single dose; Drug: Levoketoconazole 150 - 600 mg (BID); escalating dose from 150 mg to 600 mg (BID); Other Names: COR-003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) of metformin	Maximum observed plasma concentration (Cmax) of metformin with and without concomitant administration of levoketoconazole.	48 hours
Time to maximum concentration (Tmax) of metformin	Time to maximum concentration (Tmax) of metformin with and without concomitant administration of levoketoconazole.	48 hours
Area under the plasma concentration-time curve (AUC) of metformin	Area under the plasma concentration-time curve (AUC) from time 0 to time of last measurable plasma concentration (AUClast) and from time 0 extrapolated to infinity (AUCinf) of metformin with and without concomitant administration of levoketoconazole.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal clearance (CLr) of metformin	Renal clearance (CLr) of metformin with and without concomitant administration of levoketoconazole.	24 hours
Incidence of Adverse Events	Incidence of Treatment-Emergent AEs (TEAEs), AESIs, and Serious Adverse Events (SAEs). Incidence of Treatment-Emergent AEs (TEAEs), AESIs, and Serious Adverse Events (SAEs).	35 days

Collaborators and Investigators

• Sponsor: Cortendo AB

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 28, 2019
• Primary Completion (ACTUAL): May 3, 2019
• Study Completion (ACTUAL): May 3, 2019

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (ACTUAL): March 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 30, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: COR-2017-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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