Last reviewed · How we verify

NCT01054300

Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)

Completed Phase 1 Results posted Last updated 21 November 2019
What this trial tests

Phase 1 trial testing Ertugliflozin 2 mg single dose in Diabetes Mellitus, Type 2 in 52 participants. Completed in 7 April 2010.

Timeline
17 February 2010
Primary endpoint
7 April 2010
7 April 2010

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingdouble
Primary purposeother
Enrollment52
Start date17 February 2010
Primary completion7 April 2010
Estimated completion7 April 2010

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 65, any sex, with Diabetes Mellitus, Type 2 or Adult. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cumulative Urinary Glucose Excretion Over 0 to 24 Hours Primary · 0 to 24 hours after the morning dose

Urine for analysis of glucose was collected at prespecified intervals. Each participant emptied his/her bladder just before dosing, and the collection started after the morning dose (collection times: 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after the morning dose). The average amount of urinary glucose excreted from 0 to 24 hours after the morning dose is presented in the table below.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily69.4554.20 – 84.70
Cohort 1: Ertugliflozin 2 mg Once Daily70.4355.19 – 85.68
Cohort 2: Ertugliflozin 2 mg Twice Daily78.2961.87 – 94.72
Cohort 2: Ertugliflozin 4 mg Once Daily80.5464.05 – 97.02
Urinary Glucose Excretion by Time Period Primary · At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours)

Urine for analysis of glucose was collected at prespecified intervals. Each participant emptied his/her bladder just before dosing, and the collection started after the morning dose (collection times: 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after the morning dose). The average amount of urinary glucose excreted during the pre-specified time frame is presented in the table below.

0 to 4 hours post dose
GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily12.88± 14.66
Cohort 1: Ertugliflozin 2 mg Once Daily14.03± 11.63
Cohort 2: Ertugliflozin 2 mg Twice Daily14.66± 11.81
Cohort 2: Ertugliflozin 4 mg Once Daily16.34± 10.16
4 to 8 hours post dose
GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily15.42± 12.00
Cohort 1: Ertugliflozin 2 mg Once Daily17.87± 12.60
Cohort 2: Ertugliflozin 2 mg Twice Daily16.97± 11.64
Cohort 2: Ertugliflozin 4 mg Once Daily19.78± 14.02
8 to 12 hours post dose
GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily14.47± 8.84
Cohort 1: Ertugliflozin 2 mg Once Daily11.99± 7.70
Cohort 2: Ertugliflozin 2 mg Twice Daily14.30± 10.52
Cohort 2: Ertugliflozin 4 mg Once Daily12.91± 6.93
12 to 24 hours post dose
GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily26.76± 20.10
Cohort 1: Ertugliflozin 2 mg Once Daily26.31± 21.11
Cohort 2: Ertugliflozin 2 mg Twice Daily31.47± 22.71
Cohort 2: Ertugliflozin 4 mg Once Daily32.94± 21.08
24-hour Weighted Mean Plasma Glucose Primary · Up to 24 hours

Blood was collected during each treatment period at pre-dose (fasted) on Day 1 (Hour 0) and post-dose (fed) on Day 1 at 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 12.5, 13, 14, 15, 16, 18, and 24 hours.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily173.6± 26.94
Cohort 1: Ertugliflozin 2 mg Once Daily175.7± 29.88
Cohort 2: Ertugliflozin 2 mg Twice Daily169.1± 35.91
Cohort 2: Ertugliflozin 4 mg Once Daily170.4± 41.26
Weighted Mean Postprandial Plasma Glucose Primary · At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours)

The weighted mean postprandial glucose over the specified intervals were analyzed by cohort.

0 to 5 hours
GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily200.1± 38.27
Cohort 1: Ertugliflozin 2 mg Once Daily187.2± 41.37
Cohort 2: Ertugliflozin 2 mg Twice Daily194.1± 46.87
Cohort 2: Ertugliflozin 4 mg Once Daily189.9± 53.17
5 to 12 hours
GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily159.4± 25.76
Cohort 1: Ertugliflozin 2 mg Once Daily159.8± 28.46
Cohort 2: Ertugliflozin 2 mg Twice Daily160.5± 42.14
Cohort 2: Ertugliflozin 4 mg Once Daily161.5± 40.70
12 to 18 hours
GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily180.7± 35.98
Cohort 1: Ertugliflozin 2 mg Once Daily190.7± 35.38
Cohort 2: Ertugliflozin 2 mg Twice Daily182.6± 40.79
Cohort 2: Ertugliflozin 4 mg Once Daily181.9± 40.79
Fasting C-peptide Primary · Up to 24 hours (0 and 24 hours)

The fasting c-peptide was analyzed by cohort using a mixed-effects model with sequence, period, and treatment as fixed effects and participant within sequence as a random effect.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily2.822.54 – 3.11
Cohort 1: Ertugliflozin 2 mg Once Daily2.762.47 – 3.04
Cohort 2: Ertugliflozin 2 mg Twice Daily3.002.64 – 3.35
Cohort 2: Ertugliflozin 4 mg Once Daily2.992.64 – 3.34
Number of Participants Experiencing an Adverse Event Primary · Up to 16 days

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device. The table below includes all data collected since the first dose of study drug.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily5
Cohort 1: Ertugliflozin 2 mg Once Daily8
Cohort 2: Ertugliflozin 2 mg Twice Daily3
Cohort 2: Ertugliflozin 4 mg Once Daily5
Number of Participants Discontinuing Study Drug Due to an Adverse Event Primary · Up to 8 days (Day 1 in each dosing period)

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device. The table below includes all data collected since the first dose of study drug. Data include participants discontinued due to adverse events, participants with dose reduced or temporary discontinuation due to adverse events.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily0
Cohort 1: Ertugliflozin 2 mg Once Daily1
Cohort 2: Ertugliflozin 2 mg Twice Daily0
Cohort 2: Ertugliflozin 4 mg Once Daily0
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin Primary · 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose

Pharmacokinetic (PK) parameter of AUClast for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily131.8± 26
Cohort 1: Ertugliflozin 2 mg Once Daily132.7± 28
Cohort 2: Ertugliflozin 2 mg Twice Daily272± 19
Cohort 2: Ertugliflozin 4 mg Once Daily270.5± 20
Maximum Plasma Concentration (Cmax) of Ertugliflozin Primary · 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose

PK parameter of Cmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily19.51± 39
Cohort 1: Ertugliflozin 2 mg Once Daily26.98± 37
Cohort 2: Ertugliflozin 2 mg Twice Daily34.80± 23
Cohort 2: Ertugliflozin 4 mg Once Daily50.83± 25
Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin Primary · 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose

PK parameter of Tmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.

GroupValue95% CI
Cohort 1: Ertugliflozin 1 mg Twice Daily6.000.500 – 12.0
Cohort 1: Ertugliflozin 2 mg Once Daily1.000.500 – 5.50
Cohort 2: Ertugliflozin 2 mg Twice Daily6.000.500 – 8.00
Cohort 2: Ertugliflozin 4 mg Once Daily1.000.500 – 6.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 16 days (including 7-day follow-up for each period). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Ertugliflozin 1 mg Twice Daily
Serious: 0/25 (0%)
Deaths: 0/25
Cohort 1: Ertugliflozin 2 mg Once Daily
Serious: 0/26 (0%)
Deaths: 0/26
Cohort 2: Ertugliflozin 2 mg Twice Daily
Serious: 0/26 (0%)
Deaths: 0/26
Cohort 2: Ertugliflozin 4 mg Once Daily
Serious: 0/26 (0%)
Deaths: 0/26
Other adverse events (23 terms — click to expand)

ReactionSystemCohort 1: Ertugliflozin 1 …Cohort 1: Ertugliflozin 2 …Cohort 2: Ertugliflozin 2 …Cohort 2: Ertugliflozin 4 …
DiarrhoeaGastrointestinal disorders
HeadacheNervous system disorders
Eye painEye disorders
Vision blurredEye disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
FlatulenceGastrointestinal disorders
NauseaGastrointestinal disorders
VomittingGastrointestinal disorders
FatigueGeneral disorders
Wound infectionInfections and infestations
HypoglycaemiaMetabolism and nutrition disorders
Increased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
PresyncopeNervous system disorders
PollakiuriaRenal and urinary disorders
Postnasal dripRespiratory, thoracic and mediastinal disorders
EcchymosisSkin and subcutaneous tissue disorders
Skin irritationSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT01054300 adverse events section.

Sponsor's own description

This is a Phase 1 randomized, double-blind, sponsor open, 4 arm, 2 way cross-over study using 2 cohorts. The objective of the study is to evaluate the pharmacodynamics (PD) effects and the pharmacokinetic (PK) of single day dosing of 2 mg and 4 mg doses of ertugliflozin (Ertu, PF-04971729/MK-8835) each administered once vs twice daily (morning \[AM\] and evening \[PM\]) in adults with type 2 diabetes.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Population Pharmacokinetic Model for Ertugliflozin in Healthy Subjects and Patients With Type 2 Diabetes Mellitus.
    Fediuk DJ, Zhou S, Dawra VK, Sahasrabudhe V, et al · · 2021 · cited 6× · PMID 33205593 · DOI 10.1002/cpdd.885
  2. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations.
    Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, et al · · 2021 · PMID 34213819 · DOI 10.1002/cpdd.970

Verify or expand the search:

Other recruiting trials for Diabetes Mellitus, Type 2

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01054300.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing