An Investigational Drug Study in Patients With Type 2 Diabetes Mellitus (0431-024)

A Multicenter, Double-Blind, Randomized Study to Evaluate the Safety and Efficacy of the Addition of MK0431 Compared With Sulfonylurea Therapy in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Metformin Monotherapy

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00094770

Enrollment

1172

Registered

2004-10-25

Start date

2004-09-30

Completion date

2007-05-31

Last updated

2016-08-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Brief summary

The purpose of this investigational study is to determine the safety and effectiveness of an investigational drug in patients with type 2 diabetes mellitus (a specific type of diabetes).

Detailed description

The duration of treatment is 104 weeks.

Interventions

DRUGsitagliptin (MK0431)

Sitagliptin 100 mg oral tablets of sitagliptin once daily.

DRUGComparator: glipizide

Glipizide 1 tablet (5 mg) per day. Patients could then up-titrated to a total daily dose of 4 tablets twice daily (20mg/day) based on their glycemic control.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 78 Years

Healthy volunteers

Inclusion criteria

* Patients who are at least 18 years of age and not older than 78 with type 2 diabetes mellitus

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in HbA1c at Week 52	Baseline and Week 52	HbA1c is measured as percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the Week 0 HbA1c percent.

Secondary

Measure	Time frame	Description
Change From Baseline in Body Weight at Week 52	Baseline and Week 52	Change from baseline at Week 52 is defined as Week 52 minus Week 0.
Change From Baseline in Body Weight at Week 104	Baseline and Week 104	Change from baseline at Week 104 is defined as Week 104 minus Week 0.
Hypoglycemic Events at Week 52	Baseline to Week 52	Number of participants who reported 1 or more episodes of the adverse experience (AEs) of hypoglycemia.
Hypoglycemic Events at Week 104	Baseline to Week 104	Number of participants who reported 1 or more episodes of the adverse experience of hypoglycemia.
Number of Participants With Clinical Adverse Experiences (CAEs) at Week 104	Baseline to Week 104	An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.
Change From Baseline in HbA1c at Week 104	Baseline and Week 104	HbA1c is measured as percent. Thus, this change from baseline reflects the Week 104 HbA1c percent minus the Week 0 HbA1c percent.
Number of Participants With Drug-related CAEs at Week 104	Baseline to Week 104	Participants with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs.
Number of Participants With Laboratory Adverse Experiences (LAEs) at Week 104	Baseline to Week 104	A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.
Number of Participants With Serious LAEs at Week 104	Baseline to Week 104	Serious LAEs are any LAEs occurring at any dose that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer; or is an overdose.
Number of Participants With Drug-related LAEs at Week 104	Baseline to Week 104	Participants with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs.
Number of Participants With Serious CAEs at Week 104	Baseline to Week 104	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose.

Participant flow

Recruitment details

Phase III First Patient In: 26-Oct-2004; Last Patient Last Visit: 17-May-2007; 173 medical clinics worldwide.

Pre-assignment details

Participants 18-78 years of age with type 2 diabetes mellitus (T2DM) and inadequate glycemic control (Hemoglobin A1c \>6.5% and \< 10%) on metformin at a dose of \>1500mg/day.

Participants by arm

Arm	Count
Sitagliptin 100 mg The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily.	588
Glipizide The Glipizide group includes data from patients randomized to receive treatment with glipizide initiated at a dose of 1 tablet (5 mg) per day. Patients could then up-titrated to a total daily dose of 4 tablets twice daily (20mg/day) based on their glycemic control.	584
Total	1,172

Withdrawals & dropouts

Period	Reason	FG000	FG001
Year 1 ( Week 0 to Week 52)	Adverse Event	25	26
Year 1 ( Week 0 to Week 52)	Lack of Efficacy	86	58
Year 1 ( Week 0 to Week 52)	Lost to Follow-up	19	10
Year 1 ( Week 0 to Week 52)	Other	10	11
Year 1 ( Week 0 to Week 52)	Patient Moved	6	2
Year 1 ( Week 0 to Week 52)	Protocol Specified Discontinuation	19	25
Year 1 ( Week 0 to Week 52)	Protocol Violation	10	10
Year 1 ( Week 0 to Week 52)	Site Terminated	2	2
Year 1 ( Week 0 to Week 52)	Withdrawal by Subject	25	28
Year 2 (Week 0 to Week 104)	Adverse Event	35	36
Year 2 (Week 0 to Week 104)	Lack of Efficacy	180	162
Year 2 (Week 0 to Week 104)	Lost to Follow-up	25	15
Year 2 (Week 0 to Week 104)	Other	15	23
Year 2 (Week 0 to Week 104)	Patient Moved	6	2
Year 2 (Week 0 to Week 104)	Protocol Specified Discontinuation	29	30
Year 2 (Week 0 to Week 104)	Protocol Violation	13	12
Year 2 (Week 0 to Week 104)	Site Terminated	2	2
Year 2 (Week 0 to Week 104)	Withdrawal by Subject	28	38

Baseline characteristics

Characteristic	Sitagliptin 100 mg	Glipizide	Total
Age, Continuous	56.8 years STANDARD_DEVIATION 9.3	56.6 years STANDARD_DEVIATION 9.8	56.7 years STANDARD_DEVIATION 9.55
Hemoglobin A1c (HbA1c)	7.7 Percent STANDARD_DEVIATION 0.9	7.6 Percent STANDARD_DEVIATION 0.9	7.7 Percent STANDARD_DEVIATION 0.9
Race/Ethnicity, Customized Asian	50 participants	49 participants	99 participants
Race/Ethnicity, Customized Black	41 participants	35 participants	76 participants
Race/Ethnicity, Customized Hispanic	43 participants	46 participants	89 participants
Race/Ethnicity, Customized Other	22 participants	20 participants	42 participants
Race/Ethnicity, Customized White	432 participants	434 participants	866 participants
Sex: Female, Male Female	252 Participants	226 Participants	478 Participants
Sex: Female, Male Male	336 Participants	358 Participants	694 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	318 / 588	374 / 584
serious Total, serious adverse events	64 / 588	73 / 584

Outcome results

Primary

Change From Baseline in HbA1c at Week 52

HbA1c is measured as percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the Week 0 HbA1c percent.

Time frame: Baseline and Week 52

Population: The per protocol population required that a participant had measurements both at baseline and at Week 52, and did not have any major protocol violations (e.g. drug compliance \< 75%, addition of prohibited antihyperglycemic agent, incorrect double-blind study medication). No missing data were imputed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Sitagliptin 100 mg	Change From Baseline in HbA1c at Week 52	-0.67 Percent
Glipizide	Change From Baseline in HbA1c at Week 52	-0.67 Percent

Secondary

Change From Baseline in Body Weight at Week 104

Change from baseline at Week 104 is defined as Week 104 minus Week 0.

Time frame: Baseline and Week 104

Population: The All-Patient-as-Treated (APaT) population required that a participant received at least 1 dose of double-blind study therapy. No missing data were imputed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Sitagliptin 100 mg	Change From Baseline in Body Weight at Week 104	-1.6 Kilograms
Glipizide	Change From Baseline in Body Weight at Week 104	0.7 Kilograms

Secondary

Change From Baseline in Body Weight at Week 52

Change from baseline at Week 52 is defined as Week 52 minus Week 0.

Time frame: Baseline and Week 52

Population: The All-Patient-as-Treated (APaT) population required that a participant received at least 1 dose of double-blind study therapy. No missing data were imputed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Sitagliptin 100 mg	Change From Baseline in Body Weight at Week 52	-1.5 Kilograms
Glipizide	Change From Baseline in Body Weight at Week 52	1.1 Kilograms

Secondary

Change From Baseline in HbA1c at Week 104

HbA1c is measured as percent. Thus, this change from baseline reflects the Week 104 HbA1c percent minus the Week 0 HbA1c percent.

Time frame: Baseline and Week 104

Population: The per protocol population required that a participant had measurements both at baseline and at Week 104, and did not have any major protocol violations (e.g. drug compliance \< 75%, addition of prohibited antihyperglycemic agent, incorrect double-blind study medication). No missing data were imputed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Sitagliptin 100 mg	Change From Baseline in HbA1c at Week 104	-0.54 Percent
Glipizide	Change From Baseline in HbA1c at Week 104	-0.51 Percent

Secondary