Trial Outcomes & Findings for An Investigational Drug in Patients With Type 2 Diabetes Mellitus and Chronic Renal Insufficiency (0431-028)(COMPLETED) (NCT NCT00095056)

Last Updated: 2015-04-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

91 participants

Primary outcome timeframe

Week 0 through Week 12

Results posted on

2015-04-02

Participant Flow

First Patient In: 14-Dec-04 Last Patient Last Visit: 27-Jul-06 75 study centers worldwide

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.

Participant milestones

Participant milestones
Measure	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.	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.
Phase A (Weeks 0-12) STARTED	65	26
Phase A (Weeks 0-12) COMPLETED	58	25
Phase A (Weeks 0-12) NOT COMPLETED	7	1
Phase B (Weeks 12-54) STARTED	56	25
Phase B (Weeks 12-54) COMPLETED	46	20
Phase B (Weeks 12-54) NOT COMPLETED	10	5

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Phase A (Weeks 0-12) Adverse Event	1	1
Phase A (Weeks 0-12) Withdrawal by Subject	3	0
Phase A (Weeks 0-12) Death	1	0
Phase A (Weeks 0-12) Protocol specific criteria	2	0
Phase B (Weeks 12-54) Adverse Event	2	2
Phase B (Weeks 12-54) Lost to Follow-up	1	0
Phase B (Weeks 12-54) Withdrawal by Subject	2	1
Phase B (Weeks 12-54) Patient Moved	1	0
Phase B (Weeks 12-54) Death	3	1
Phase B (Weeks 12-54) Protocol specific criteria	1	0
Phase B (Weeks 12-54) Protocol Violation	0	1

Baseline Characteristics

An Investigational Drug in Patients With Type 2 Diabetes Mellitus and Chronic Renal Insufficiency (0431-028)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=65 Participants 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.	Placebo n=26 Participants 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.	Total n=91 Participants Total of all reporting groups
Age, Continuous	68.9 years STANDARD_DEVIATION 9.8 • n=5 Participants	65.3 years STANDARD_DEVIATION 9.7 • n=7 Participants	67.9 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	10 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	16 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized White	22 participants n=5 Participants	8 participants n=7 Participants	30 participants n=5 Participants
Race/Ethnicity, Customized Black	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	17 participants n=5 Participants	9 participants n=7 Participants	26 participants n=5 Participants
Race/Ethnicity, Customized Asian	20 participants n=5 Participants	7 participants n=7 Participants	27 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
HbA1c (Hemoglobin A1c)	7.6 Percent STANDARD_DEVIATION 0.9 • n=5 Participants	7.8 Percent STANDARD_DEVIATION 0.9 • n=7 Participants	7.7 Percent STANDARD_DEVIATION 0.9 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sitagliptin n=65 Participants 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.	Placebo n=26 Participants 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.
Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment With CAEs	41 Participants	16 Participants
Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment With drug-related CAEs	8 Participants	1 Participants
Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment With serious CAEs	9 Participants	1 Participants
Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment With LAEs	9 Participants	5 Participants
Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment With drug-related LAEs	1 Participants	0 Participants
Safety and Tolerability of Sitagliptin After 12 Weeks of Treatment With serious LAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 0 through Week 54

Outcome measures

Outcome measures
Measure	Sitagliptin n=65 Participants 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.	Placebo n=26 Participants 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.
Safety and Tolerability of Sitagliptin Over 54 Weeks With CAEs	50 Participants	22 Participants
Safety and Tolerability of Sitagliptin Over 54 Weeks With drug-related CAEs	8 Participants	5 Participants
Safety and Tolerability of Sitagliptin Over 54 Weeks With serious CAEs	20 Participants	10 Participants
Safety and Tolerability of Sitagliptin Over 54 Weeks With LAEs	15 Participants	8 Participants
Safety and Tolerability of Sitagliptin Over 54 Weeks With drug-related LAEs	2 Participants	0 Participants
Safety and Tolerability of Sitagliptin Over 54 Weeks With serious LAEs	0 Participants	0 Participants

Adverse Events

Sitagliptin

Serious events: 20 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Executive Vice President, Clinical and Quantitative Sciences

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sitagliptin n=65 participants at risk 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.	Placebo n=26 participants at risk 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.
Blood and lymphatic system disorders Anaemia	3.1% 2/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Gastrointestinal disorders Constipation	1.5% 1/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Gastrointestinal disorders Diarrhoea	9.2% 6/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	15.4% 4/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	1.5% 1/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
General disorders Oedema Peripheral	3.1% 2/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Catheter Site Infection	0.00% 0/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Nasopharyngitis	6.2% 4/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	3.8% 1/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Upper Respiratory Tract Infection	7.7% 5/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	19.2% 5/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Urinary Tract Infection	7.7% 5/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	11.5% 3/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Investigations Blood Creatinine Increased	1.5% 1/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Investigations Blood Glucose Increased	4.6% 3/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	11.5% 3/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Metabolism and nutrition disorders Hypoglycaemia	4.6% 3/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	23.1% 6/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Musculoskeletal and connective tissue disorders Back Pain	1.5% 1/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Musculoskeletal and connective tissue disorders Shoulder Pain	0.00% 0/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	7.7% 2/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Nervous system disorders Dizziness	6.2% 4/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	3.8% 1/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 4/65 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.	3.8% 1/26 • Week 0 through Week 54 Patients received rescue medication if they met specific glycemic goals. This summary of SAEs includes events that occurred either before or after receiving rescue medication. This summary of Other AEs includes only those AEs that occurred prior to a patient receiving rescue medication.