Trial Outcomes & Findings for GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy (GETGOAL-MONO Japan LTS) (NCT NCT00905255)

Last Updated: 2016-12-21

Results Overview

Overview of adverse event profile is reported in terms of percentage of patients with treatment emergent adverse events (TEAEs) during the 24-week treatment period: any TEAE; any serious TEAE; any TEAE leading to death; and any TEAE leading to permanent treatment discontinuation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

69 participants

Primary outcome timeframe

First dose of study drug up to 3 days after the last dose of study drug at Week 24 or early withdrawal

Results posted on

2016-12-21

Participant Flow

The study was conducted at 9 centers in Japan between May 09, 2009 and January 22, 2011. The overall duration of treatment was at least 76 weeks (52-week open-label treatment; 24-week open-label extension treatment).

A total of 75 patients were screened of which 6(8.0%) were screen failures; main reasons for screen failure:glycosylated hemoglobin being out of defined protocol range (\>=7% and \<=10%) and use of an antidiabetic agent other than a sulfonylurea or alpha-glucosidase inhibitor within 3 months prior to screening. A total of 69 patients were randomized.

Participant milestones

Participant milestones
Measure	Lixisenatide (Two-step Titration) 2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to end of treatment.
Overall Study STARTED	33	36
Overall Study Safety Population	33	36
Overall Study Modified Intent-to-Treat(mITT)Population	33	36
Overall Study COMPLETED	20	27
Overall Study NOT COMPLETED	13	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Lixisenatide (Two-step Titration) 2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to end of treatment.
Overall Study Adverse Event	7	5
Overall Study Withdrawal by Subject	5	4
Overall Study Familial and Personal Reasons	1	0

Baseline Characteristics

GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy (GETGOAL-MONO Japan LTS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lixisenatide (Two-step Titration) n=33 Participants 2-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (One-step Titration) n=36 Participants 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to end of treatment.	Total n=69 Participants Total of all reporting groups
Age, Continuous	56.9 years STANDARD_DEVIATION 9.0 • n=5 Participants	60.4 years STANDARD_DEVIATION 8.2 • n=7 Participants	58.7 years STANDARD_DEVIATION 8.7 • n=5 Participants
Gender Female	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Gender Male	30 Participants n=5 Participants	28 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized Race: Asian/Oriental	33 participants n=5 Participants	36 participants n=7 Participants	69 participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Non Hispanic	33 participants n=5 Participants	36 participants n=7 Participants	69 participants n=5 Participants
Glycosylated Hemoglobin (HbA1c)	8.35 percentage of hemoglobin STANDARD_DEVIATION 0.82 • n=5 Participants	8.12 percentage of hemoglobin STANDARD_DEVIATION 0.68 • n=7 Participants	8.23 percentage of hemoglobin STANDARD_DEVIATION 0.76 • n=5 Participants
Fasting Plasma Glucose (FPG)	9.91 millimole per liter (mmol/L) STANDARD_DEVIATION 1.91 • n=5 Participants	9.16 millimole per liter (mmol/L) STANDARD_DEVIATION 1.92 • n=7 Participants	9.52 millimole per liter (mmol/L) STANDARD_DEVIATION 1.94 • n=5 Participants
Body Weight	70.75 kilogram (kg) STANDARD_DEVIATION 19.21 • n=5 Participants	66.74 kilogram (kg) STANDARD_DEVIATION 11.14 • n=7 Participants	68.66 kilogram (kg) STANDARD_DEVIATION 15.54 • n=5 Participants
Body Mass Index (BMI)	25.16 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.27 • n=5 Participants	24.81 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.68 • n=7 Participants	24.98 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.48 • n=5 Participants
Duration of Diabetes	8.05 years STANDARD_DEVIATION 6.38 • n=5 Participants	9.03 years STANDARD_DEVIATION 7.87 • n=7 Participants	8.56 years STANDARD_DEVIATION 7.16 • n=5 Participants

PRIMARY outcome

Timeframe: First dose of study drug up to 3 days after the last dose of study drug at Week 24 or early withdrawal

Population: Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=33 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) n=36 Participants 1-step initiation regimen of lixisenatide.
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of the One-Step and Two-Step Titration Arms Assessed Through Adverse Events Collection and Vital Signs, Electrocardiogram (ECG) and Laboratory Monitoring Any TEAE	81.8 percentage of participants	88.9 percentage of participants
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of the One-Step and Two-Step Titration Arms Assessed Through Adverse Events Collection and Vital Signs, Electrocardiogram (ECG) and Laboratory Monitoring Any Serious TEAE	6.1 percentage of participants	0 percentage of participants
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of the One-Step and Two-Step Titration Arms Assessed Through Adverse Events Collection and Vital Signs, Electrocardiogram (ECG) and Laboratory Monitoring Any TEAE Leading to Death	0 percentage of participants	0 percentage of participants
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of the One-Step and Two-Step Titration Arms Assessed Through Adverse Events Collection and Vital Signs, Electrocardiogram (ECG) and Laboratory Monitoring Any TEAE Leading to Treatment Discontinuation	9.1 percentage of participants	11.1 percentage of participants

SECONDARY outcome

Timeframe: First dose of study drug up to 3 days after the last dose of study drug at Week 76 or early withdrawal

Population: Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered. Analysis was done on the overall group (pooled data from the 2-step and 1-step titration arms) as pre-specified

Overview of adverse event profile is reported in terms of percentage of patients with TEAEs during the on-treatment period: any TEAE; any serious TEAE; any TEAE leading to death; any TEAE leading to permanent treatment discontinuation. The on-treatment period was the time from the first dose of study drug up to 3 days after the last dose at Week 76.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=69 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of All Patients During On-Treatment Period Assessed Through Adverse Events Collection and Vital Signs, ECG and Laboratory Monitoring Any TEAE	91.3 percentage of participants	—
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of All Patients During On-Treatment Period Assessed Through Adverse Events Collection and Vital Signs, ECG and Laboratory Monitoring Any Serious TEAE	4.3 percentage of participants	—
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of All Patients During On-Treatment Period Assessed Through Adverse Events Collection and Vital Signs, ECG and Laboratory Monitoring Any TEAE Leading to Death	0 percentage of participants	—
Overview of Adverse Event Profile (Treatment Emergent Adverse Events) of All Patients During On-Treatment Period Assessed Through Adverse Events Collection and Vital Signs, ECG and Laboratory Monitoring Any TEAE Leading to Treatment Discontinuation	14.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, Week 52, 76

Population: mITT population. Number of patients analyzed=patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period and "n" = patients with HbA1c assessment for the specified category. Analysis was done on the overall group (pooled data from the 2-step and 1-step titration arms) as pre-specified

Absolute change = HbA1c value at week of assessment (Week 52/Week 76) minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=47 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) for All Patients at Week 52 and 76 Week 52 (n=47, observed cases)	-0.83 percentage of hemoglobin Standard Deviation 0.96	—
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) for All Patients at Week 52 and 76 Week 76 (n=33, observed cases)	-0.72 percentage of hemoglobin Standard Deviation 1.20	—

SECONDARY outcome

Timeframe: Week 52, 76

The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=47 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 52 and 76 Week 52 (n=47, observed cases)	40.4 percentage of participants	—
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 52 and 76 Week 76 (n=33, observed cases)	27.3 percentage of participants	—

SECONDARY outcome

Timeframe: Week 52, 76

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=47 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 52 and 76 Week 52 (n=47, observed cases)	14.9 percentage of participants	—
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 52 and 76 Week 76 (n=33, observed cases)	18.2 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, Week 52, 76

Population: mITT population. Number of patients analyzed=patients with baseline and at least 1 post-baseline weight assessment during on-treatment period and "n" = patients with weight assessment for the specified category. Analysis was done on the overall group (pooled data from the 2-step and 1-step titration arms) as pre-specified

Change was calculated by subtracting baseline value from value at week of assessment (Week 52/Week 76). The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=47 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Change From Baseline in Body Weight for All Patients at Week 52 and 76 Week 52 (n=47, observed cases)	-1.67 kilogram Standard Deviation 2.10	—
Change From Baseline in Body Weight for All Patients at Week 52 and 76 Week 76 (n=33, observed cases)	-1.58 kilogram Standard Deviation 2.15	—

SECONDARY outcome

Timeframe: Baseline, Week 52, 76

Population: mITT population. Number of patients analyzed=patients with baseline and at least 1 post-baseline FPG assessment during on-treatment period and "n" = patients with FPG assessment for the specified category. Analysis was done on the overall group (pooled data from the 2-step and 1-step titration arms) as pre-specified

Change was calculated by subtracting baseline value from value at week of assessment (Week 52/Week 76). The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=47 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Change From Baseline in Fasting Plasma Glucose (FPG) for All Patients at Week 52 and 76 Week 52 (n=47, observed cases)	-0.96 mmol/L Standard Deviation 1.54	—
Change From Baseline in Fasting Plasma Glucose (FPG) for All Patients at Week 52 and 76 Week 76 (n=33, observed cases)	-0.46 mmol/L Standard Deviation 2.08	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 52, Baseline up to Week 76

Population: mITT population.Analysis was done on the overall group (pooled data from the 2-step and 1-step titration arms) as pre-specified

Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) were performed. Threshold values - from Week 4 to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%, from Week 24 to end of treatment (Week 76): fasting SMPG/FPG \>180 mg/dL (10.0 mmol/L) or HbA1c \>8%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=69 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Percentage of Patients Requiring Rescue Therapy Baseline up to Week 52	17.4 percentage of participants	—
Percentage of Patients Requiring Rescue Therapy Baseline up to Week 76	23.2 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose of study drug up to 3 days after the last dose of study drug at Week 24 or early withdrawal

Population: Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose less than 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=33 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) n=36 Participants 1-step initiation regimen of lixisenatide.
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for the One-Step and Two-Step Titration Arms During 24-Week Treatment Period Symptomatic Hypoglycemia	2 participants	1 participants
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for the One-Step and Two-Step Titration Arms During 24-Week Treatment Period Severe Symptomatic Hypoglycemia	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose of study drug up to 3 days after the last dose of study drug at Week 76 or early withdrawal

Outcome measures

Outcome measures
Measure	Lixisenatide (Combined) n=69 Participants Included all patients who received 2-step initiation regimen of lixisenatide or 1-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide.
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for All Patients During On-Treatment Period Symptomatic hypoglycemia	5 participants	—
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia for All Patients During On-Treatment Period Severe symptomatic hypoglycemia	0 participants	—

Adverse Events

Lixisenatide (Two-step Titration)

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Lixisenatide (One-step Titration)

Serious events: 1 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lixisenatide (Two-step Titration) n=33 participants at risk 2-step initiation regimen of lixisenatide.	Lixisenatide (One-step Titration) n=36 participants at risk 1-step initiation regimen of lixisenatide.
Infections and infestations Gastroenteritis	3.0% 1/33 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/36 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Eye disorders Cataract	0.00% 0/33 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.8% 1/36 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/33 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.8% 1/36 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Skin laceration	3.0% 1/33 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/36 • First dose of study drug up to 3 days after the last dose administration up to week 76 Median exposure to study treatment was 531 and 533 days in lixisenatide two-step titration and lixisenatide one-step titration arms, respectively. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER