A Phase 1 Study of Ertugliflozin in Healthy Male Participants (MK-8835-020)

NCT ID: NCT02411929

Last Updated: 2018-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-29
• Study Completion Date: 2015-02-09

Brief Summary

This study will evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of ertugliflozin following oral administration of unlabeled ertugliflozin (MK-8835) and intravenous (IV) and oral administration of 14^C-labeled ertugliflozin in healthy male participants.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ertugliflozin

Period 1: Oral dose of 15 mg unlabeled ertugliflozin + intravenous (IV) dose of 100 µg 14\^C-labeled ertugliflozin containing approximately 400 nCi 14\^C. The 14\^C IV dose will be administered as an infusion over approximately 5 minutes starting at 55 minutes after the unlabeled oral dose. → Period 2: Oral dose 15 mg unlabeled ertugliflozin + oral dose of 100 µg 14\^C-labeled ertugliflozin containing approximately 400 nCi 14\^C. Both the unlabeled and 14\^C-ertugliflozin will be administered at the same time (no more than 5 minutes apart). Dosing in Periods 1 and 2 will be separated by a washout of at least 11 days.

Group Type: EXPERIMENTAL

Unlabeled ertugliflozin for oral use

Intervention Type: DRUG

15 mg oral (3 x 5 mg tablets)

14^C-labeled ertugliflozin for IV use

Intervention Type: DRUG

100 µg (10 µg/mL solution IV) containing approximately 400 nCi 14\^C (ie, radiolabeled ertugliflozin)

14^C-labeled ertugliflozin for oral use

Intervention Type: DRUG

100 µg (10 µg/mL solution oral) containing approximately 400 nCi 14\^C (ie, radiolabeled ertugliflozin)

Interventions

Unlabeled ertugliflozin for oral use

15 mg oral (3 x 5 mg tablets)

Intervention Type: DRUG

14^C-labeled ertugliflozin for IV use

100 µg (10 µg/mL solution IV) containing approximately 400 nCi 14\^C (ie, radiolabeled ertugliflozin)

Intervention Type: DRUG

14^C-labeled ertugliflozin for oral use

100 µg (10 µg/mL solution oral) containing approximately 400 nCi 14\^C (ie, radiolabeled ertugliflozin)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male subjects between the ages of 18 and 65 years.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m^2; and a total body weight >50 kg (110 lbs.)

Exclusion Criteria

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies).
• Any clinically significant malabsorption condition (eg, gastrectomy, bowel resection).
• A positive urine drug screen for drugs of abuse or recreational drugs.
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
• History of abuse of alcohol or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
• Current smokers and those who have smoked any substance within the last 12 months.
• Treatment with an investigational drug within 1 month preceding the first dose of study medication.
• Have participated in any clinical study with exposure to 14^C in the last 12 months.
• Any radiation exposure, including that which is projected to result from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures. No occupationally exposed worker, as defined in the Ionising Radiation Regulation 1999, shall participate in the study.
• Use of prescription or nonprescription drugs (including vitamins and dietary supplements) within 7 days prior to the first dose of study medication.
• Use of herbal supplements within 28 days prior to the first dose of study medication.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
• Participants who have previously participated in a clinical trial for ertugliflozin.
• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Raje S, Callegari E, Sahasrabudhe V, Vaz A, Shi H, Fluhler E, Woolf EJ, Schildknegt K, Matschke K, Alvey C, Zhou S, Papadopoulos D, Fountaine R, Saur D, Terra SG, Stevens L, Gaunt D, Cutler DL. Novel Application of the Two-Period Microtracer Approach to Determine Absolute Oral Bioavailability and Fraction Absorbed of Ertugliflozin. Clin Transl Sci. 2018 Jul;11(4):405-411. doi: 10.1111/cts.12549. Epub 2018 Mar 25.

Reference Type: RESULT

PMID: 29575530 (View on PubMed)

Marshall JC, Liang Y, Sahasrabudhe V, Tensfeldt T, Fediuk DJ, Zhou S, Krishna R, Dawra VK, Wood LS, Sweeney K. Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure. J Clin Pharmacol. 2021 Sep;61(9):1220-1231. doi: 10.1002/jcph.1866. Epub 2021 Jun 19.

Reference Type: DERIVED

PMID: 33813736 (View on PubMed)

Other Identifiers

B1521043

Identifier Type: OTHER

Identifier Source: secondary_id

8835-020

Identifier Type: -

Identifier Source: org_study_id