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
Overview
- Phase
- Phase 1
- Intervention
- Metformin 500 mg Oral Tablet
- Conditions
- Healthy Subjects
- Sponsor
- Cortendo AB
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Maximum observed plasma concentration (Cmax) of metformin
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •18-55 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.
Exclusion Criteria
- •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 -
Arms & Interventions
Metformin Only
Intervention: Metformin 500 mg Oral Tablet
Levoketoconazole Only
Intervention: Levoketoconazole 150 - 600 mg (BID)
Levoketoconazole + Metformin
Intervention: Metformin 500 mg Oral Tablet
Levoketoconazole + Metformin
Intervention: Levoketoconazole 150 - 600 mg (BID)
Outcomes
Primary Outcomes
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.
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.
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 Outcomes
- Renal clearance (CLr) of metformin(24 hours)
- Incidence of Adverse Events(35 days)