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| ID | Type | Description | Link |
|---|---|---|---|
| B1521007 | Other Identifier | Pfizer Protocol Number | |
| MK-8835-040 | Other Identifier | Merck Protocol Number |
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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Ertu 2 mg/Placebo (Pbo)→Ertu 1 mg/Ertu 1 mg | Experimental | Period 1: Ertu 2 mg in the AM and Pbo in the PM for 1 day. Period 2: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
|
| Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo | Experimental | Period 1: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
|
| Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg | Experimental | Period 1: Ertu 4 mg in the AM and Pbo in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
|
| Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/Pbo | Experimental | Period 1: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. Period 2: Ertu 4 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ertugliflozin 2 mg single dose | Drug | Ertugliflozin 2 mg dose (two 1 mg strength tablets), administered as a single dose |
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| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Urinary Glucose Excretion Over 0 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 from 0 to 24 hours after the morning dose is presented in the table below. | 0 to 24 hours after the morning dose |
| Urinary Glucose Excretion by Time Period | 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. | At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours) |
| 24-hour Weighted Mean Plasma Glucose | 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. | Up to 24 hours |
| Weighted Mean Postprandial Plasma Glucose | The weighted mean postprandial glucose over the specified intervals were analyzed by cohort. | At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours) |
| Fasting Plasma Glucose | Blood samples were to be collected following a fast from all food and drink (except water) for at least 8 hours. Fasting Plasma Glucose was collected as part of the assessment of weighted mean 24-hour plasma glucose. As such, it was not specified as an endpoint in the Statistical Analysis Plan and was not analyzed or summarized separately. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30802200 | Result | Dawra VK, Liang Y, Shi H, Bass A, Hickman A, Terra SG, Zhou S, Cutler D, Sahasrabudhe V. A PK/PD study comparing twice-daily to once-daily dosing regimens of ertugliflozin in healthy subjects . Int J Clin Pharmacol Ther. 2019 Apr;57(4):207-216. doi: 10.5414/CP203343. | |
| 34213819 | Derived | Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: Ertu 2 mg/Pbo→Ertu 1 mg/Ertu 1 mg | Period 1: Ertugliflozin (Ertu) 2 mg in the AM and placebo (Pbo) in the PM for 1 day. Period 2: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
| FG001 | Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Ertugliflozin 2 mg split into twice daily | Drug | Ertugliflozin 1 mg dose (1 mg strength tablet) administered twice daily x 1 day |
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| Ertugliflozin 4 mg single dose | Drug | Ertugliflozin 4 mg dose (four 1 mg strength tablets), administered as a single dose |
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| Ertugliflozin 4 mg split into twice daily | Drug | Ertugliflozin 2 mg dose (two 1 mg strength tablets) administered twice daily x 1 day |
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| Placebo | Drug | Placebo to ertugliflozin administered as a single dose |
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| Up to 24 hours |
| Fasting C-peptide | 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. | Up to 24 hours (0 and 24 hours) |
| Number of Participants Experiencing an Adverse Event | 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. | Up to 16 days |
| Number of Participants Discontinuing Study Drug Due to an Adverse Event | 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. | Up to 8 days (Day 1 in each dosing period) |
| Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin | Pharmacokinetic (PK) parameter of AUClast for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis. | 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose |
| Maximum Plasma Concentration (Cmax) of Ertugliflozin | PK parameter of Cmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis. | 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose |
| Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin | PK parameter of Tmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis. | 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose |
Period 1: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
| FG002 | Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg | Period 1: Ertu 4 mg in the AM and Pbo in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
| FG003 | Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/P | Period 1: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. Period 2: Ertu 4 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2. |
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| NOT COMPLETED |
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| Period 2 |
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All randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Period 1: participants received a total daily dose of ertugliflozin 2 mg for 1 day; Period 2: participants received a total daily dose of ertugliflozin 2 mg for 1 day |
| BG001 | Cohort 2 | Period 1: participants received a total daily dose of ertugliflozin 4 mg; Period 2: participants received a total daily dose of ertugliflozin 4 mg for 1 day |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | Participants |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative Urinary Glucose Excretion Over 0 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 from 0 to 24 hours after the morning dose is presented in the table below. | Analysis population included randomized participants who received assigned dose and had urine collection during all of the collection time frames between 0 and 24 hours following the morning dose. | Posted | Least Squares Mean | 90% Confidence Interval | Grams | 0 to 24 hours after the morning dose |
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| Primary | Urinary Glucose Excretion by Time Period | 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. | Analysis population included randomized participants who received assigned dose and had urine collection during the specific time frame. | Posted | Mean | Standard Deviation | Grams | At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours) |
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| Primary | 24-hour Weighted Mean Plasma Glucose | 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. | Analysis population included randomized participants who received study drug and had mean plasma glucose measurements during all of the specific collection time frames. | Posted | Mean | Standard Deviation | mg/dL | Up to 24 hours |
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| Primary | Weighted Mean Postprandial Plasma Glucose | The weighted mean postprandial glucose over the specified intervals were analyzed by cohort. | Analysis population included randomized participants who received assigned dose and had postprandial plasma glucose measurements during the specific time frame. | Posted | Mean | Standard Deviation | mg/dL | At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours) |
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| Primary | Fasting Plasma Glucose | Blood samples were to be collected following a fast from all food and drink (except water) for at least 8 hours. Fasting Plasma Glucose was collected as part of the assessment of weighted mean 24-hour plasma glucose. As such, it was not specified as an endpoint in the Statistical Analysis Plan and was not analyzed or summarized separately. | The protocol listed fasting plasma glucose as one of the endpoints of the study. However, given the assessment of weighted mean 24-hour plasma glucose and weighted mean postprandial glucose following the 3 meals on Day 1 of each period, analysis of fasting plasma glucose was not undertaken. | Posted | Up to 24 hours |
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| Primary | Fasting C-peptide | 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. | Analysis population included randomized participants who received assigned dose and had fasting c-peptide measurements during the specific time frame. | Posted | Least Squares Mean | 90% Confidence Interval | ng/mL | Up to 24 hours (0 and 24 hours) |
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| Primary | Number of Participants Experiencing an Adverse Event | 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. | Analysis population includes all treated participants. | Posted | Count of Participants | Participants | Up to 16 days |
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| Primary | Number of Participants Discontinuing Study Drug Due to an Adverse Event | 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. | Analysis population includes all treated participants. | Posted | Count of Participants | Participants | Up to 8 days (Day 1 in each dosing period) |
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| Primary | Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin | Pharmacokinetic (PK) parameter of AUClast for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis. | All participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose |
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| Primary | Maximum Plasma Concentration (Cmax) of Ertugliflozin | PK parameter of Cmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis. | All participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose |
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| Primary | Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin | PK parameter of Tmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis. | All participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. | Posted | Median | Full Range | hours | 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose |
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Up to 16 days (including 7-day follow-up for each period)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: Ertugliflozin 1 mg Twice Daily | Participants received ertugliflozin 1 mg twice daily for 1 day | 0 | 25 | 0 | 25 | 5 | 25 |
| EG001 | Cohort 1: Ertugliflozin 2 mg Once Daily | Participants received ertugliflozin 2 mg once daily for 1 day | 0 | 26 | 0 | 26 | 8 | 26 |
| EG002 | Cohort 2: Ertugliflozin 2 mg Twice Daily | Participants received ertugliflozin 2 mg twice daily for 1 day | 0 | 26 | 0 | 26 | 3 | 26 |
| EG003 | Cohort 2: Ertugliflozin 4 mg Once Daily | Participants received ertugliflozin 4 mg once daily for 1 day | 0 | 26 | 0 | 26 | 5 | 26 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye pain | Eye disorders | MedDRA 13.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 13.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Vomitting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
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| Increased appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
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| Postnasal drip | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
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Institution will provide manuscripts, abstracts, or the full text of any other intended disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to Pfizer at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, Institution agrees to delay the disclosure for a period not to exceed an additional 60 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C570288 | ertugliflozin |
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| Title | Measurements |
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| 65 years or older |
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| Male |
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| Cohort 2: Ertugliflozin 4 mg Once Daily |
Participants received ertugliflozin 4 mg once daily for 1 day |
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Participants received ertugliflozin 4 mg once daily for 1 day |
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| Units | Counts |
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Participants received ertugliflozin 4 mg once daily for 1 day
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Participants received ertugliflozin 4 mg once daily for 1 day
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