A Multiple Dose Study Of Ertugliflozin (PF-04971729, MK-8835) In Otherwise Healthy Overweight And Obese Volunteers (MK-8835-037)

NCT01018823 | Completed Phase 1

• 1 other identifier: 8835-037
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

Ertugliflozin (PF-04971729, MK-8835) is under development for the treatment of Type 2 Diabetes. The primary purpose of this trial is to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, of multiple oral doses of ertugliflozin.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (17)

• Number of Participants Experiencing an Adverse Event (AE)

  Up to 28 days postdose (Up to 42 days)

• Number of Participants Discontinuing Study Drug Due to an AE

  Up to 14 days

• Area under the plasma concentration-time curve (AUC) over the dosing interval tau (AUCtau) for ertugliflozin

  Up to 17 days

• Maximum plasma concentration (Cmax) of ertugliflozin

  Up to 17 days

• Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin

  Up to 17 days

• Ertugliflozin half life (t1/2)

  Up to 17 Days

• Apparent clearance (CL/F) after a single dose of ertugliflozin

  Up to 17 days

• Apparent volume of distribution (Vz/F)

  Up to 17 days

• Observed Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac[obs])

  Up to 17 days

• Change from baseline in 24-hour weighted mean glucose

  Baseline and Day 14

• Change from baseline in 24-hour urinary glucose excretion

  Baseline and Day 14

• Change from baseline in 24-hour plasma C-peptide

  Baseline and Day 14

• Inhibition of glucose reabsorption

  Baseline and Day 14

• Change from baseline in body weight

  Baseline and Day 14

• Area under the plasma concentration-time curve over 8 hours (AUC[0-8]) for serum intact parathyroid hormone

  Up to 17 days

• Area under the plasma concentration-time curve over 24 hours (AUC[0-24]) for serum intact parathyroid hormone

  Up to 17 days

• Trough concentration of serum intact parathyroid hormone (Ctrough)

  Up to 17 days

Study Arms (5)

Ertugliflozin 1 mg

EXPERIMENTAL

Ertugliflozin 1 mg, oral, once daily for 14 days

Drug: Ertugliflozin

Ertugliflozin up to 5 mg

EXPERIMENTAL

Ertugliflozin up to 5 mg, oral, once daily for 14 days

Drug: Ertugliflozin

Ertugliflozin up to 25 mg

EXPERIMENTAL

Ertugliflozin up to 25 mg, oral, once daily for 14 days

Drug: Ertugliflozin

Ertugliflozin up to 100 mg

EXPERIMENTAL

Ertugliflozin up to 100 mg, once daily for 14 days

Drug: Ertugliflozin

Placebo

PLACEBO COMPARATOR

Placebo to Ertugliflozin once daily for 14 days

Drug: Placebo to Ertugliflozin

Interventions

Ertugliflozin DRUG

Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast

Also known as: PF-04971729, MK-8835

Ertugliflozin 1 mg; Ertugliflozin up to 100 mg; Ertugliflozin up to 25 mg; Ertugliflozin up to 5 mg

Placebo to Ertugliflozin DRUG

Placebo oral dosing solutions/suspensions administered once daily for 14 days immediately after breakfast

Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive.
• Body Mass Index (BMI) of 26.5 to 35.5 kg/m2; and a total body weight \>50 kg (110 lbs).

You may not qualify if:

• 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 at time of dosing).
• Evidence of glycosuria, as defined by a positive urine dipstick test; Fasting (at least 10 hours) serum triglyceride \>300 mg/dL; Fasting (at least 10 hours) LDL-cholesterol \>190 mg/dL; Fasting (at least 10 hours) serum 25-OH Vitamin D concentration \<20 ng/mL

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Pfizer: collaborator

Related Publications (2)

• Fediuk DJ, Nucci G, Dawra VK, Cutler DL, Amin NB, Terra SG, Boyd RA, Krishna R, Sahasrabudhe V. Overview of the Clinical Pharmacology of Ertugliflozin, a Novel Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor. Clin Pharmacokinet. 2020 Aug;59(8):949-965. doi: 10.1007/s40262-020-00875-1.

  PMID: 32337660 RESULT

• 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.

  PMID: 33813736 DERIVED

MeSH Terms

Interventions

ertugliflozin

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2009
• First Posted: November 25, 2009
• Study Start: December 14, 2009
• Primary Completion: March 18, 2010
• Study Completion: March 18, 2010
• Last Updated: May 29, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share