Clinical trial NCT01018823: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2009-11-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 28 days postdose (Up to 42 days)
measure: Number of Participants Discontinuing Study Drug Due to an AE
timeFrame: Up to 14 days
measure: Area under the plasma concentration-time curve (AUC) over the dosing interval tau (AUCtau) for ertugliflozin
timeFrame: Up to 17 days
measure: Maximum plasma concentration (Cmax) of ertugliflozin
timeFrame: Up to 17 days
measure: Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin
timeFrame: Up to 17 days
measure: Ertugliflozin half life (t1/2)
timeFrame: Up to 17 Days
measure: Apparent clearance (CL/F) after a single dose of ertugliflozin
timeFrame: Up to 17 days
measure: Apparent volume of distribution (Vz/F)
timeFrame: Up to 17 days
measure: Observed Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac[obs])
timeFrame: Up to 17 days
measure: Change from baseline in 24-hour weighted mean glucose
timeFrame: Baseline and Day 14
measure: Change from baseline in 24-hour urinary glucose excretion
timeFrame: Baseline and Day 14
measure: Change from baseline in 24-hour plasma C-peptide
timeFrame: Baseline and Day 14
measure: Inhibition of glucose reabsorption
timeFrame: Baseline and Day 14
measure: Change from baseline in body weight
timeFrame: Baseline and Day 14
measure: Area under the plasma concentration-time curve over 8 hours (AUC[0-8]) for serum intact parathyroid hormone
timeFrame: Up to 17 days
measure: Area under the plasma concentration-time curve over 24 hours (AUC[0-24]) for serum intact parathyroid hormone
timeFrame: Up to 17 days
measure: Trough concentration of serum intact parathyroid hormone (Ctrough)
timeFrame: Up to 17 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.
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.