Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01096667 | Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042) | PHASE2 | COMPLETED | 194 | — | — | May 17, 2010 | Feb 25, 2011 | Sep 13, 2018 | - | — |
| NCT01059825 | Study Of Safety And Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-016) | PHASE2 | COMPLETED | 375 | — | — | Feb 24, 2010 | Jan 20, 2011 | Sep 13, 2018 | - | — |
| NCT01223339 | Evaluation of Pharmacokinetics, Safety, And Tolerability Of Ertugliflozin (PF-04971729, MK-8835) In Japanese And Western Healthy Participants (MK-8835-041) | PHASE1 | COMPLETED | 24 | — | — | Oct 1, 2010 | Feb 1, 2011 | May 20, 2016 | - | — |
| NCT01054300 | Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040) | PHASE1 | COMPLETED | 52 | — | — | Feb 17, 2010 | Apr 7, 2010 | Nov 21, 2019 | - | — |
Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).
Change from baseline on 24-hour average SBP at Week 4 assessed using 24-hour ABPM. In the case of missing data, last observation carried forward (LOCF).
HbA1c is measured as percent.
HbA1c is measured as percent. The change from baseline is the Week 12 HbA1c percent minus the Week 0 HbA1c percent (last observation carried forward \[LOCF\]).
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.
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.
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.
The weighted mean postprandial glucose over the specified intervals were analyzed by cohort.
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 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.
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.
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.
Pharmacokinetic (PK) parameter of AUClast for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
PK parameter of Cmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
PK parameter of Tmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Placebo to ertugliflozin (resembling either 1 mg or 5 mg), placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days. |
| Ertugliflozin 1 mg | EXPERIMENTAL | Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days |
| Ertugliflozin 5 mg | EXPERIMENTAL | Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days |
| Ertugliflozin 25 mg | EXPERIMENTAL | Ertugliflozin 25 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to HCTZ once daily for 28 days |
| HCTZ 12.5mg | ACTIVE_COMPARATOR | HCTZ 12.5 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to ertugliflozin (resembling 25 mg) once daily for 28 days |
| Ertugliflozin 10 mg | EXPERIMENTAL | Ertugliflozin 10 mg, placebo for ertugliflozin (25 mg), and placebo to sitagliptin, oral, once daily for 84 days |
| Sitagliptin 100 mg | ACTIVE_COMPARATOR | Sitagliptin 100 mg, placebo for ertugliflozin (1 mg or 5 mg and 25 mg), oral, once daily for 84 days |
| Single Dose Japanese Cohort | EXPERIMENTAL | This will be a single dose Cohort in which Japanese healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin or placebo through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration. |
| Single dose Western cohort | EXPERIMENTAL | This will be a single dose Cohort in which Western healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration. |
| Multiple Dose Japanese Cohort | EXPERIMENTAL | This will be a multiple dose Cohort in which Japanese healthy participants will receive once-daily 25 mg ertugliflozin or placebo for 7 days. |
| 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 |
|---|---|---|
| Placebo to Ertuglilflozin 1 or 5 mg | DRUG | Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days |
| Ertugliflozin 1 mg | DRUG | Ertugliflozin tablet 1 mg once daily for 28 days |
| Ertugliflozin 5 mg | DRUG | Ertugliflozin tablet 5 mg once daily for 28 days |
| Ertugliflozin 25 mg | DRUG | Ertugliflozin tablet 25 mg once daily for 28 days |
| HCTZ 12.5mg | DRUG | Hydrocholorthiazide (HCTZ) 12.5 mg capsule once daily for 28 days |
| Placebo to HCTZ | DRUG | Placebo to HCTZ 12.5 mg capsule once daily for 28 days |
| Placebo to ertuglilflozin 25 mg | DRUG | Placebo to ertuglilflozin tablet 25 mg once daily for 28 days |
| Placebo to Ertugliflozin | DRUG | Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days |
| Sitagliptin 100 mg | DRUG | Tablet, 100 mg, once daily for 84 days |
| Placebo to Sitagliptin | DRUG | Tablet, matching placebo to 100 mg, once daily for 84 days |
| Metformin | DRUG | Participants continued pre-study stable doses of metformin during the run-in and treatment periods of the study (maximum dose up to 2500 mg/day or 3000 mg/day where the maximum metformin dose per the local country product labels was 3000 mg/day). |
| Ertugliflozin | DRUG | Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state |
| Placebo | DRUG | Placebo tablets to Ertugliflozin administered in the fasted state |
| Ertugliflozin 2 mg single dose | DRUG | Ertugliflozin 2 mg dose (two 1 mg strength tablets), administered as a single dose |
| Ertugliflozin 2 mg split into twice daily | DRUG | Ertugliflozin 1 mg dose (1 mg strength tablet) administered twice daily x 1 day |
| Ertugliflozin 4 mg single dose | DRUG | Ertugliflozin 4 mg dose (four 1 mg strength tablets), administered as a single dose |
| Ertugliflozin 4 mg split into twice daily | DRUG | Ertugliflozin 2 mg dose (two 1 mg strength tablets) administered twice daily x 1 day |
Inclusion Criteria: * Participants with type 2 diabetes and hypertension * Medically stable * On at least 1 (and up to 2) oral diabetes drugs * And up to 2 medicines for blood pressure control Exclusion Criteria: * Participants with type 1 diabetes * Heart attack * Stroke * Uncontrolled blood pre...