Diabetes Mellitus, Type 2, Chronic Renal Insufficiency
Conditions
Keywords
Type 2 Diabetes Mellitus and Chronic Renal Insufficiency
Brief summary
The purpose of this study is to determine the safety and tolerability of an investigational drug in patients with Type 2 Diabetes Mellitus (a specific type of diabetes) and Chronic Renal Insufficiency (inadequate kidney function).
Interventions
DRUGsitagliptin
One (participants with visit 1 estimated creatinine clearance \<30 mL/min or undergo regular dialysis) or Two (participants with visit 1 creatinine clearance of =30 to \<50 mL/min; not on dialysis) tablets of 25 mg Sitagliptin daily.
One (participants with visit 1 estimated creatinine clearance \<30 mL/min or undergo regular dialysis) or Two (participants with visit 1 creatinine clearance of =30 to \<50 mL/min and not on dialysis) tablets of placebo to sitagliptin 25 mg daily.
DRUGglipizide
One 5 mg glipizide tablet per day. The dose of glipizide administered per day may be increased after 2 weeks and at 2-week intervals thereafter up to 20 mg based upon fingerstick glucose determinations.
One placebo to glipizide 5 mg tablet per day. The dose of placebo to glipizide administered per day may be increased after 2 weeks and at 2-week intervals thereafter up to 20 mg based upon fingerstick glucose determinations.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are at least 18 years of age diagnosed with type 2 diabetes mellitus (T2DM) (a specific type of diabetes). * Patient has renal (kidney) insufficiency (inadequate kidney function)
Exclusion criteria
* Patient has had heart problems (such as a heart attack or chest pain) or stroke within the past 6 months or any condition or therapy which, in the opinion of the investigator, may not be in the patient's best interest to participate. * Pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | Week 0 through Week 12 | Safety and tolerability were measured in terms of the number of patients with clinical adverse experiences (CAEs), serious CAEs, drug-related CAEs, laboratory adverse experiences (LAEs), serious LAEs, and drug-related LAEs. Drug-relationship was assessed by the study investigator according to his/her best clinical judgment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Sitagliptin Over 54 Weeks | Week 0 through Week 54 | Safety and tolerability were measured in terms of the number of patients with clinical adverse experiences (CAEs), serious CAEs, drug-related CAEs, laboratory adverse experiences (LAEs), serious LAEs, and drug-related LAEs. Drug-relationship was assessed by the study investigator according to his/her best clinical judgment. |
Participant flow
Recruitment details
First Patient In: 14-Dec-04 Last Patient Last Visit: 27-Jul-06 75 study centers worldwide
Pre-assignment details
Patients ≥18 years of age with chronic renal insufficiency and type 2 diabetes mellitus who had an A1C of 6.5-10% (not on baseline insulin therapy) or 7.5-10% (on baseline insulin therapy) after an antihyperglycemic agent (AHA) wash-off period of up to 12 weeks, were eligible to enter the 54-week study.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin The Sitagliptin group includes data from patients randomized to receive treatment with either one (1) 25 mg oral tablet of sitagliptin once daily (blinded) \[patients with Creatinine Clearance (CrCl) \<30 mL/min or dialysis\] or two (2) 25 mg oral tablets of sitagliptin once daily (blinded) \[patients with CrCl 30 to \<50mL/min\] alone or in combination with baseline insulin therapy. During Phase B, patients in the Sitagliptin group (with the exception of patients on baseline insulin therapy and patients who received glycemic rescue medication in Phase A) were given glipizide placebo (blinded). During Phase B, patients on baseline insulin could have their insulin uptitrated, and patients who received glycemic rescue medication in Phase A continued on open-label rescue medication. | 65 |
| Placebo The Placebo group includes data from patients randomized to receive treatment with either one (1) tablet of placebo matching sitagliptin 25 mg (blinded) \[patients with CrCl \<30 mL/min or dialysis\] or two (2) tablets of placebo matching sitagliptin 25 mg (blinded) \[patients with CrCl 30 to \<50mL/min\] alone or in combination with baseline insulin therapy. During Phase B, patients in the Placebo group (with the exception of patients on baseline insulin therapy and patients who received glycemic rescue medication in Phase A) were given glipizide (blinded). During Phase B, patients on baseline insulin could have their insulin uptitrated, and patients who received glycemic rescue medication in Phase A continued on open-label rescue medication. | 26 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase A (Weeks 0-12) | Adverse Event | 1 | 1 |
| Phase A (Weeks 0-12) | Death | 1 | 0 |
| Phase A (Weeks 0-12) | Protocol specific criteria | 2 | 0 |
| Phase A (Weeks 0-12) | Withdrawal by Subject | 3 | 0 |
| Phase B (Weeks 12-54) | Adverse Event | 2 | 2 |
| Phase B (Weeks 12-54) | Death | 3 | 1 |
| Phase B (Weeks 12-54) | Lost to Follow-up | 1 | 0 |
| Phase B (Weeks 12-54) | Patient Moved | 1 | 0 |
| Phase B (Weeks 12-54) | Protocol specific criteria | 1 | 0 |
| Phase B (Weeks 12-54) | Protocol Violation | 0 | 1 |
| Phase B (Weeks 12-54) | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Sitagliptin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 68.9 years STANDARD_DEVIATION 9.8 | 65.3 years STANDARD_DEVIATION 9.7 | 67.9 years STANDARD_DEVIATION 9.8 |
| HbA1c (Hemoglobin A1c) | 7.6 Percent STANDARD_DEVIATION 0.9 | 7.8 Percent STANDARD_DEVIATION 0.9 | 7.7 Percent STANDARD_DEVIATION 0.9 |
| Race/Ethnicity, Customized Asian | 20 participants | 7 participants | 27 participants |
| Race/Ethnicity, Customized Black | 4 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized Hispanic | 17 participants | 9 participants | 26 participants |
| Race/Ethnicity, Customized Other | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized White | 22 participants | 8 participants | 30 participants |
| Sex: Female, Male Female | 34 Participants | 10 Participants | 44 Participants |
| Sex: Female, Male Male | 31 Participants | 16 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 65 | 20 / 26 |
| serious Total, serious adverse events | 20 / 65 | 10 / 26 |
Outcome results
Primary
Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment
Safety and tolerability were measured in terms of the number of patients with clinical adverse experiences (CAEs), serious CAEs, drug-related CAEs, laboratory adverse experiences (LAEs), serious LAEs, and drug-related LAEs. Drug-relationship was assessed by the study investigator according to his/her best clinical judgment.
Time frame: Week 0 through Week 12
Population: All patients who took study medication were included in the analysis. Events that occurred after initiation of glycemic rescue therapy were excluded from the analysis of CAEs, drug-related CAEs, LAEs, \& drug-related LAEs. Events that occurred after initiation of glycemic rescue therapy were included in the analysis of serious CAEs and serious LAEs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitagliptin | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With CAEs | 41 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With drug-related CAEs | 8 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With serious CAEs | 9 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With LAEs | 9 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With drug-related LAEs | 1 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With serious LAEs | 0 Participants |
| Placebo | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With drug-related LAEs | 0 Participants |
| Placebo | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With CAEs | 16 Participants |
| Placebo | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With LAEs | 5 Participants |
| Placebo | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With drug-related CAEs | 1 Participants |
| Placebo | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With serious LAEs | 0 Participants |
| Placebo | Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment | With serious CAEs | 1 Participants |
Secondary
Safety and Tolerability of Sitagliptin Over 54 Weeks
Safety and tolerability were measured in terms of the number of patients with clinical adverse experiences (CAEs), serious CAEs, drug-related CAEs, laboratory adverse experiences (LAEs), serious LAEs, and drug-related LAEs. Drug-relationship was assessed by the study investigator according to his/her best clinical judgment.
Time frame: Week 0 through Week 54
Population: All patients who took study medication were included in the analysis. Events that occurred after initiation of glycemic rescue therapy were excluded from the analysis of CAEs, drug-related CAEs, LAEs, \& drug-related LAEs. Events that occurred after initiation of glycemic rescue therapy were included in the analysis of serious CAEs and serious LAEs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitagliptin | Safety and Tolerability of Sitagliptin Over 54 Weeks | With CAEs | 50 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin Over 54 Weeks | With drug-related CAEs | 8 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin Over 54 Weeks | With serious CAEs | 20 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin Over 54 Weeks | With LAEs | 15 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin Over 54 Weeks | With drug-related LAEs | 2 Participants |
| Sitagliptin | Safety and Tolerability of Sitagliptin Over 54 Weeks | With serious LAEs | 0 Participants |
| Placebo | Safety and Tolerability of Sitagliptin Over 54 Weeks | With drug-related LAEs | 0 Participants |
| Placebo | Safety and Tolerability of Sitagliptin Over 54 Weeks | With CAEs | 22 Participants |
| Placebo | Safety and Tolerability of Sitagliptin Over 54 Weeks | With LAEs | 8 Participants |
| Placebo | Safety and Tolerability of Sitagliptin Over 54 Weeks | With drug-related CAEs | 5 Participants |
| Placebo | Safety and Tolerability of Sitagliptin Over 54 Weeks | With serious LAEs | 0 Participants |
| Placebo | Safety and Tolerability of Sitagliptin Over 54 Weeks | With serious CAEs | 10 Participants |