Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Drug Interaction Study of Levoketoconazole and Metformin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03880825
Recruitment Status : Active, not recruiting
First Posted : March 19, 2019
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Cortendo AB

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.

Condition or disease Intervention/treatment Phase
Healthy Subjects Drug: Metformin 500 mg Oral Tablet Drug: Levoketoconazole 150 - 600 mg (BID) Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: 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
Actual Study Start Date : March 28, 2019
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Metformin Only Drug: Metformin 500 mg Oral Tablet
single dose

Levoketoconazole Only Drug: Levoketoconazole 150 - 600 mg (BID)
escalating dose from 150 mg to 600 mg (BID)
Other Name: COR-003

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 Name: COR-003




Primary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) of metformin [ Time Frame: 48 hours ]
    Maximum observed plasma concentration (Cmax) of metformin with and without concomitant administration of levoketoconazole.

  2. Time to maximum concentration (Tmax) of metformin [ Time Frame: 48 hours ]
    Time to maximum concentration (Tmax) of metformin with and without concomitant administration of levoketoconazole.

  3. Area under the plasma concentration-time curve (AUC) of metformin [ Time Frame: 48 hours ]
    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.


Secondary Outcome Measures :
  1. Renal clearance (CLr) of metformin [ Time Frame: 24 hours ]
    Renal clearance (CLr) of metformin with and without concomitant administration of levoketoconazole.

  2. Incidence of Adverse Events [ Time Frame: 35 days ]

    Incidence of Treatment-Emergent AEs (TEAEs), AESIs, and Serious Adverse Events (SAEs).

    Incidence of Treatment-Emergent AEs (TEAEs), AESIs, and Serious Adverse Events (SAEs).




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03880825


Locations
Layout table for location information
United States, Florida
Clinical Pharmacology of Miami, LLC
Miami, Florida, United States, 33014
Sponsors and Collaborators
Cortendo AB
Investigators
Layout table for investigator information
Study Director: Steven Schoenfeld, MD Cortendo AB

Layout table for additonal information
Responsible Party: Cortendo AB
ClinicalTrials.gov Identifier: NCT03880825     History of Changes
Other Study ID Numbers: COR-2017-03
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs