To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c - Study Results

To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c (LEAD-3)

This study has been terminated.

( Trial was terminated at week 195 due to an insufficient number of subjects remaining to obtain reasonable statistical power )

Study NCT00294723 Information provided by Novo Nordisk

First Received on February 20, 2006. Last Updated on September 22, 2011 History of Changes

Results First Received: February 23, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Diabetes Mellitus, Type 2
Interventions:	Drug: liraglutide Drug: glimepiride Drug: placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 138 centres in two countries: United States of America (USA) (126) and Mexico (12).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects with type 2 diabetes treated with diet/exercise or OAD (Oral Anti-Diabetic Drug) monotherapy for at least 2 months were eligible. One subject randomised to the liraglutide 1.8 mg group was withdrawn from the study prior to dosing due to protocol non compliance, subject was not included in the intent-to-treat (ITT) or safety analysis sets.

Reporting Groups

	Description
Lira 1.8	Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)
Lira 1.2	Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)
Glimepiride	Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)

Participant Flow for 3 periods

Period 1: Double-Blind Period 52 Weeks

	Lira 1.8	Lira 1.2	Glimepiride
STARTED	247 ^[1]	251 ^[1]	248 ^[1]
Exposed to Study Drug	246 ^[2]	251	248
COMPLETED	173	162	152
NOT COMPLETED	74	89	96
Adverse Event	18	25	15
Lack of Efficacy	9	15	25
Protocol Violation	11	11	5
Not specified in study report	36	38	51

[1]	Randomised
[2]	Subject withdrew before exposure to drug, and thus not included in the safety and ITT analysis sets

Period 2: Open-Label Extension 52 Weeks

	Lira 1.8	Lira 1.2	Glimepiride
STARTED	154 ^[1]	149 ^[2]	137 ^[3]
COMPLETED	114	110	97
NOT COMPLETED	40	39	40
Adverse Event	5	5	2
Lack of Efficacy	12	15	21
Protocol Violation	4	3	3
Not specified in study report	19	16	14

[1]	19 subjects did not continue into the extension period
[2]	13 subjects did not continue into the extension period
[3]	15 subjects did not continue into the extension period

Period 3: Additional Open-Label Extension 91 Weeks

	Lira 1.8	Lira 1.2	Glimepiride
STARTED	62 ^[1]	53 ^[2]	28 ^[3]
COMPLETED	34	32	8
NOT COMPLETED	28	21	20
Adverse Event	1	1	0
Lack of Efficacy	24	14	16
Protocol Violation	1	1	1
Not specified in study report	2	5	3

[1]	52 subjects did not continue into the extension period
[2]	57 subjects did not continue into the extension period
[3]	69 subjects did not continue into the extension period

Baseline Characteristics

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Reporting Groups

	Description
Lira 1.8	Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195)
Lira 1.2	Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195)
Glimepiride	Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195)

Baseline Measures

	Lira 1.8	Lira 1.2	Glimepiride	Total
Number of Participants [units: participants]	247	251	248	746
Age [units: participants]
<=18 years	0	0	0	0
Between 18 and 65 years	222	208	208	638
>=65 years	25	43	40	108
Age [units: years] Mean ± Standard Deviation	52.0 ± 10.8	53.7 ± 11.0	53.4 ± 10.9	53.0 ± 10.9
Gender [units: participants]
Female	126	134	115	375
Male	121	117	133	371
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	87	81	93	261
Not Hispanic or Latino	160	170	155	485
Unknown or Not Reported	0	0	0	0
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0	0	0	0
Asian	12	5	9	26
Native Hawaiian or Other Pacific Islander	2	0	0	2
Black or African American	30	34	30	94
White	186	200	192	578
More than one race	0	0	0	0
Unknown or Not Reported	17	12	17	46
Region of Enrollment [units: participants]
Mexico	52	53	66	171
United States	195	198	182	575
Previous anti-diabetic treatment [units: participants]
Diet/Exercise	87	91	94	272
Monotherapy	160	160	154	474
Body Mass Index (BMI) [units: kg/m^2] Mean ± Standard Deviation	32.8 ± 6.3	33.2 ± 5.6	33.2 ± 5.6	33.1 ± 5.8
Duration of diabetes ^[1] [units: years] Mean ± Standard Deviation	5.3 ± 5.1	5.2 ± 5.5	5.6 ± 5.1	5.4 ± 5.3
HbA1c (Glycosylated Haemoglobin A1c) ^[2] [units: percentage of total haemoglobin] Mean ± Standard Deviation	8.3 ± 1.1	8.3 ± 1.0	8.4 ± 1.2	8.3 ± 1.1

[1]	Number of years since diagnosis
[2]	HbA1c at screening

Outcome Measures

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1. Primary:

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 [ Time Frame: week 0, week 52 ]

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2. Primary:

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104 [ Time Frame: week 0, week 104 ]

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3. Primary:

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156 [ Time Frame: week 0, week 156 ]

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4. Secondary:

Change in Body Weight at Week 52 [ Time Frame: week 0, week 52 ]

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5. Secondary:

Change in Body Weight at Week 104 [ Time Frame: week 0, week 104 ]

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6. Secondary:

Change in Body Weight at Week 156 [ Time Frame: week 0, week 156 ]

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7. Secondary:

Change in Fasting Plasma Glucose at Week 52 [ Time Frame: week 0, week 52 ]

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8. Secondary:

Change in Fasting Plasma Glucose at Week 104 [ Time Frame: week 0, week 104 ]

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9. Secondary:

Change in Fasting Plasma Glucose at Week 156 [ Time Frame: week 0, week 156 ]

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10. Secondary:

Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 [ Time Frame: week 0, week 52 ]

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11. Secondary:

Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 [ Time Frame: week 0, week 104 ]

Show Outcome Measure 11

12. Secondary:

Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 [ Time Frame: week 0, week 156 ]

Show Outcome Measure 12

13. Secondary:

Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 [ Time Frame: week 0, week 52 ]

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14. Secondary:

Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 [ Time Frame: week 0, week 104 ]

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15. Secondary:

Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 [ Time Frame: week 0, week 156 ]

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16. Secondary:

Hypoglycaemic Episodes [ Time Frame: weeks 0-104 ]

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17. Secondary:

Hypoglycaemic Episodes [ Time Frame: weeks 104-195 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Novo Nordisk reserves the right to not release data until specified milestones. This includes the right to not release interim results, because the release of such information can invalidate the results of the entire trial. At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Trial terminated due to an insufficient number of subjects remaining to obtain reasonable statistical power. Efficacy data was not analysed after week 156. Safety data was collected through week 195. No data was available from week 195 to 260

Results Point of Contact:

Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com

No publications provided by Novo Nordisk

Publications automatically indexed to this study:

Buse JB, Garber A, Rosenstock J, Schmidt WE, Brett JH, Videbæk N, Holst J, Nauck M. Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab. 2011 Jun;96(6):1695-702. Epub 2011 Mar 30.

Hegedüs L, Moses AC, Zdravkovic M, Le Thi T, Daniels GH. GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J Clin Endocrinol Metab. 2011 Mar;96(3):853-60. Epub 2011 Jan 5.

Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B; LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009 Feb 7;373(9662):473-81. Epub 2008 Sep 24.

Responsible Party:	Novo Nordisk
ClinicalTrials.gov Identifier:	NCT00294723 History of Changes
Obsolete Identifiers:	NCT00853359
Other Study ID Numbers:	NN2211-1573
Study First Received:	February 20, 2006
Results First Received:	February 23, 2010
Last Updated:	September 22, 2011
Health Authority:	Mexico: Federal Commission for Protection Against Health Risks; United States: Food and Drug Administration