Drug Interaction Study of Levoketoconazole and Metformin

NCT03880825 | Completed Phase 1 FDA Drug

• 1 other identifier: COR-2017-03
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Renal clearance (CLr) of metformin

  24 hours

• Incidence of Adverse Events

  35 days

Study Arms (3)

Metformin Only

OTHER

Drug: Metformin 500 mg Oral Tablet

Levoketoconazole Only

OTHER

Drug: Levoketoconazole 150 - 600 mg (BID)

Levoketoconazole + Metformin

OTHER

Drug: Metformin 500 mg Oral Tablet; Drug: Levoketoconazole 150 - 600 mg (BID)

Interventions

Metformin 500 mg Oral Tablet DRUG

single dose

Levoketoconazole + Metformin; Metformin Only

Levoketoconazole 150 - 600 mg (BID) DRUG

escalating dose from 150 mg to 600 mg (BID)

Also known as: COR-003

Levoketoconazole + Metformin; Levoketoconazole Only

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years of age, inclusive, at time of consent.
• Body mass index (BMI) between 18 and 32 kg/m2, inclusive.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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).
• Concurrent medical illness that would interfere with the conduct of the study in the opinion of the Investigator.
• 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.
• Clinically significant ECG abnormality or confirmed QTcF interval \> 450 msec at Screening or unconfirmed QTcF interval \> 450 msec at CRU admission.
• Family history (parents, siblings, and offspring) of QT interval sudden cardiac death.
• 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.
• Positive urinary cotinine test at Screening.
• 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.
• Positive for Human Immunodeficiency Virus (HIV), hepatitis B, and/or hepatitis C on Screening assessments.
• Acute illness within 7 days of the first CRU admission on Day -1.
• Donated plasma within 7 days of Screening.
• Donated 1 or more pints of blood (or equivalent blood loss) within 30 days prior to Screening.
• 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.
• 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.
• Female subject who is pregnant or lactating.

Sponsors & Collaborators

• Cortendo AB: lead

Study Sites (1)

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

MeSH Terms

Interventions

Metformin; Tablets; BID protein, human

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Steven Schoenfeld, MD

  Cortendo AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 19, 2019
• Study Start: March 28, 2019
• Primary Completion: May 3, 2019
• Study Completion: May 3, 2019
• Last Updated: August 30, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)