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

Primary Purpose

Healthy Volunteer

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Ertugliflozin

Placebo to Ertugliflozin

About this trial

This is an interventional other trial for Healthy Volunteer

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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).

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 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

Ertugliflozin 1 mg

Ertugliflozin up to 5 mg

Ertugliflozin up to 25 mg

Ertugliflozin up to 100 mg

Placebo

Arm Description

Ertugliflozin 1 mg, oral, once daily for 14 days

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

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

Ertugliflozin up to 100 mg, once daily for 14 days

Placebo to Ertugliflozin once daily for 14 days

Outcomes

Primary Outcome Measures

Number of Participants Experiencing an Adverse Event (AE)

Number of Participants Discontinuing Study Drug Due to an AE

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

Maximum plasma concentration (Cmax) of ertugliflozin

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

Ertugliflozin half life (t1/2)

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

Apparent volume of distribution (Vz/F)

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

Change from baseline in 24-hour weighted mean glucose

Change from baseline in 24-hour urinary glucose excretion

Change from baseline in 24-hour plasma C-peptide

Inhibition of glucose reabsorption

Change from baseline in body weight

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

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

Trough concentration of serum intact parathyroid hormone (Ctrough)

Secondary Outcome Measures

Full Information

NCT ID

NCT01018823

First Posted

November 23, 2009

Last Updated

May 28, 2020

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01018823

Brief Title

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

Official Title

A Phase 1, Randomized, Placebo-Controlled, Parallel Group, 14 Day Repeated Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-04971729 In Otherwise Healthy Overweight And Obese Adult Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

December 14, 2009 (Actual)

Primary Completion Date

March 18, 2010 (Actual)

Study Completion Date

March 18, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

Collaborators

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

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.

Detailed Description

To evaluate the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics, of multiple oral doses of ertugliflozin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy Volunteer

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ertugliflozin 1 mg

Arm Type

Experimental

Arm Description

Ertugliflozin 1 mg, oral, once daily for 14 days

Arm Title

Ertugliflozin up to 5 mg

Arm Type

Experimental

Arm Description

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

Arm Title

Ertugliflozin up to 25 mg

Arm Type

Experimental

Arm Description

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

Arm Title

Ertugliflozin up to 100 mg

Arm Type

Experimental

Arm Description

Ertugliflozin up to 100 mg, once daily for 14 days

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo to Ertugliflozin once daily for 14 days

Intervention Type

Drug

Intervention Name(s)

Ertugliflozin

Other Intervention Name(s)

PF-04971729, MK-8835

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo to Ertugliflozin

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants Experiencing an Adverse Event (AE)

Time Frame

Up to 28 days postdose (Up to 42 days)

Title

Number of Participants Discontinuing Study Drug Due to an AE

Time Frame

Up to 14 days

Title

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

Time Frame

Up to 17 days

Title

Maximum plasma concentration (Cmax) of ertugliflozin

Time Frame

Up to 17 days

Title

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

Time Frame

Up to 17 days

Title

Ertugliflozin half life (t1/2)

Time Frame

Up to 17 Days

Title

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

Time Frame

Up to 17 days

Title

Apparent volume of distribution (Vz/F)

Time Frame

Up to 17 days

Title

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

Time Frame

Up to 17 days

Title

Change from baseline in 24-hour weighted mean glucose

Time Frame

Baseline and Day 14

Title

Change from baseline in 24-hour urinary glucose excretion

Time Frame

Baseline and Day 14

Title

Change from baseline in 24-hour plasma C-peptide

Time Frame

Baseline and Day 14

Title

Inhibition of glucose reabsorption

Time Frame

Baseline and Day 14

Title

Change from baseline in body weight

Time Frame

Baseline and Day 14

Title

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

Time Frame

Up to 17 days

Title

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

Time Frame

Up to 17 days

Title

Trough concentration of serum intact parathyroid hormone (Ctrough)

Time Frame

Up to 17 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Citations:

PubMed Identifier

32337660

Citation

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.

Results Reference

result

PubMed Identifier

33813736

Citation

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.

Results Reference

derived

Learn more about this trial

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

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