A Phase 3 interventional study of Insulin glargine/lixisenatide Fixed Ratio Combination and Insulin glargine (HOE901) in Type 2 Diabetes, sponsored by Sanofi. Completed at 273 sites in 23 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-05-09.
Sponsored by Sanofi · Phase 3, Interventional, and Treatment
Primary Objective:
To compare the insulin glargine/lixisenatide fixed ratio combination to lixisenatide alone and to insulin glargine alone (on top of metformin treatment) in glycated hemoglobin (HbA1c) change from baseline to Week 30.
Secondary Objective:
To compare the overall efficacy and safety of insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine alone and to lixisenatide alone (on top of metformin treatment) over a 30 week treatment period in participants with type 2 diabetes.
Approximately 37 weeks including up to 6 weeks of screening, 30-week treatment period, and a 3 days follow-up period.
9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.
This study's enrollment of 1,170 is above the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →Sanofi is the lead sponsor of 1,547 studies on the registry; 88 are open to participants now.
Of its 204 completed or terminated interventional studies of FDA-regulated products, 122 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
HbA1c at screening visit:
Exclusion Criteria for randomization at the end of the screening period:
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
FRC once daily (QD) for 30 weeks. Dose individually adjusted.
Drug: Insulin glargine/lixisenatide Fixed Ratio Combination · Drug: Metformin
Insulin glargine QD for 30 weeks. Dose individually adjusted.
Drug: Insulin glargine (HOE901) · Drug: Metformin
Lixisenatide 10 mcg QD for 2 weeks, then 20 mcg QD (maintenance dose).
Drug: Lixisenatide (AVE0010) · Drug: Metformin
Insulin glargine/Lixisenatide FRC was self-administered by subcutaneous (SC) injection in the morning within one hour before breakfast using one of the 2 prefilled disposable SoloStar® pen-injectors: Pen A containing 100 U/mL insulin glargine (Lantus, 100 U/mL) and 50 mcg/mL lixisenatide in a ratio of 2 U:1 mcg, used for administration of doses from 10 U to 40 U (10 U/5mcg to 40 U/20mcg). Pen B containing 100 U/mL insulin glargine (Lantus, 100 U/mL) and 33 mcg/mL lixisenatide in a ratio of 3 U:1 mcg, used to administer doses from 41 U to 60 U (41 U/13 mcg to 60 U/20 mcg). The starting dose was 10 U/5 mcg. Dose was then adjusted individually to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L) while avoiding hypoglycemia.
Also known as: (HOE901/AVE0010)
Insulin glargine (100 U/mL) was self-administered by SC injection at approximately the same time every day. Dose was adjusted individually to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L) while avoiding hypoglycemia.
Also known as: Lantus
Lixisenatide was self-administered by SC injection within 0 to 60 minutes before breakfast or evening meal. If the maintenance dose of 20 mcg was not tolerated, dose could be reduced to 10 mcg.
Also known as: Lyxumia
Pharmaceutical form: Tablet; Route of administration: Oral administration.
Change in HbA1c From Baseline to Week 30
Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine. Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30
Participants without Week 30 value for HbA1c were counted as non-responders.
Time frame: Week 30
Change in Plasma Glucose Excursion From Baseline to Week 30
Plasma glucose excursion = 2-hour postprandial plasma glucose (PPG) value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 30 value. Missing data was imputed using last observation carried forward (LOCF).
Time frame: Baseline, Week 30
Change in Body Weight From Baseline to Week 30
Change in body weight was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 30
Change in FPG was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30
Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime two times in a week before baseline, before visit Week 12 and before visit Week 30 and the average value across the profiles performed in the week before a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 30 value. The analysis included all scheduled measurements obtained during the study. The missing data was handled by mixed effect model with repeated measures (MMRM) approach.
Time frame: Baseline, Week 30
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30
Time frame: Week 30
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
Time frame: Baseline up to Week 30
Average Daily Insulin Glargine Dose at Week 30
The analysis included scheduled measurements obtained up to the date of last injection of the IMP, including those obtained after introduction of rescue therapy.
Time frame: Week 30
Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to Week 30
The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 30 value. Missing data was imputed using LOCF.
Time frame: Baseline, Week 30
Percentage of Participants Reaching HbA1c <7.0% at Week 30 With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L). The analysis included all HbA1c measurements at Week 30, including those obtained after the IMP discontinuation or the introduction of rescue medication.
Time frame: Baseline up to Week 30
Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period
Routine fasting 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) was performed. Threshold values - from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8%.
Time frame: Baseline up to Week 30
Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year
Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
Time frame: First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)
Percentage of Participants With Documented Symptomatic Hypoglycemia
Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
Time frame: First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)
Percentage of Participants With Severe Symptomatic Hypoglycemia
Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Plasma glucose measurements might not have been available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal was considered sufficient evidence that the event had been induced by a low plasma glucose concentration. Severe symptomatic hypoglycemia included all episodes in which neurological impairment was severe enough to prevent self-treatment, and which were thus thought to place participants at risk of injury to themselves or others.
Time frame: First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)
The study was conducted at 240 centers in 23 countries. A total of 2457 participants were screened between February 12, 2014 and September 16, 2014. 978 participants were not eligible for run-in mainly due to glycosylated hemoglobin (HbA1c) value at screening visit being out of the protocol defined range.
| Milestone | Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Started | 469 | 467 | 234 |
| Treated | 469 | 467 | 233 |
| Completed | 440 | 440 | 205 |
| Not completed | 29 | 27 | 29 |
| Withdrew: Randomized but not treated | 0 | 0 | 1 |
| Withdrew: Adverse event | 12 | 9 | 21 |
| Withdrew: Lack of efficacy | 1 | 0 | 3 |
| Withdrew: Poor compliance to protocol | 8 | 9 | 4 |
| Withdrew: Other than specified | 8 | 9 | 0 |
Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine. Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
| percentage of hemoglobin | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Change in HbA1c From Baseline to Week 30 | -1.63 ± 0.038 | -1.34 ± 0.039 | -0.85 ± 0.052 |
Participants without Week 30 value for HbA1c were counted as non-responders.
| percentage of participants | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| HbA1c <7.0% | 73.7 | 59.4 | 33 |
| HbA1c ≤6.5% | 55.8 | 39.5 | 19.3 |
Plasma glucose excursion = 2-hour postprandial plasma glucose (PPG) value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 30 value. Missing data was imputed using last observation carried forward (LOCF).
| mmol/L | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Change in Plasma Glucose Excursion From Baseline to Week 30 | -2.31 ± 0.154 | -0.18 ± 0.157 | -3.23 ± 0.216 |
Change in body weight was calculated by subtracting baseline value from Week 30 value.
| kg | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Change in Body Weight From Baseline to Week 30 | -0.29 ± 0.182 | 1.11 ± 0.183 | -2.3 ± 0.256 |
Change in FPG was calculated by subtracting baseline value from Week 30 value.
| mmol/L | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 30 | -3.46 ± 0.09 | -3.27 ± 0.091 | -1.5 ± 0.124 |
Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime two times in a week before baseline, before visit Week 12 and before visit Week 30 and the average value across the profiles performed in the week before a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 30 value. The analysis included all scheduled measurements obtained during the study. The missing data was handled by mixed effect model with repeated measures (MMRM) approach.
| mmol/L | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30 | -3.35 ± 0.081 | -2.66 ± 0.084 | -1.95 ± 0.111 |
| percentage of participants | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 | 43.2 | 25.1 | 27.9 |
Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).
| percentage of participants | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period | 31.8 | 18.9 | 26.2 |
The analysis included scheduled measurements obtained up to the date of last injection of the IMP, including those obtained after introduction of rescue therapy.
| Units (U) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine |
|---|---|---|
| Average Daily Insulin Glargine Dose at Week 30 | 39.77 ± 0.699 | 40.46 ± 0.701 |
The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 30 value. Missing data was imputed using LOCF.
| mmol/L | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to Week 30 | -5.68 ± 0.176 | -3.31 ± 0.178 | -4.58 ± 0.245 |
Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L). The analysis included all HbA1c measurements at Week 30, including those obtained after the IMP discontinuation or the introduction of rescue medication.
| percentage of participants | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Percentage of Participants Reaching HbA1c <7.0% at Week 30 With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period | 53.6 | 44.4 | 30.5 |
Routine fasting 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) was performed. Threshold values - from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8%.
| percentage of participants | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period | 3.6 | 3.4 | 12.4 |
Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
| Events per subject-year | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year | 1.44 | 1.22 | 0.34 |
Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
| percentage of participants | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Percentage of Participants With Documented Symptomatic Hypoglycemia | 25.6 | 23.6 | 6.4 |
Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Plasma glucose measurements might not have been available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal was considered sufficient evidence that the event had been induced by a low plasma glucose concentration. Severe symptomatic hypoglycemia included all episodes in which neurological impairment was severe enough to prevent self-treatment, and which were thus thought to place participants at risk of injury to themselves or others.
| percentage of participants | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| Percentage of Participants With Severe Symptomatic Hypoglycemia | 0 | 0.2 | 0 |
Collected over All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Insulin Glargine/Lixisenatide Fixed Ratio Combination | — | 18/469 (3.8%) | 138/469 (29.4%) |
| Insulin Glargine | — | 19/467 (4.1%) | 85/467 (18.2%) |
| Lixisenatide | — | 9/233 (3.9%) | 98/233 (42.1%) |
| Event | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| ErysipelasInfections and infestations | 1/469 | 0/467 | 1/233 |
| Meningitis staphylococcalInfections and infestations | 0/469 | 0/467 | 1/233 |
| Lung neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/469 | 0/467 | 1/233 |
| Metastases to liverNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/469 | 0/467 | 1/233 |
| Anaphylactic reactionImmune system disorders | 0/469 | 0/467 | 1/233 |
| Diabetes mellitus inadequate controlMetabolism and nutrition disorders | 0/469 | 0/467 | 1/233 |
| Metabolic acidosisMetabolism and nutrition disorders | 0/469 | 0/467 | 1/233 |
| Transient ischaemic attackNervous system disorders | 1/469 | 0/467 | 1/233 |
| RadiculopathyNervous system disorders | 0/469 | 0/467 | 1/233 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 0/469 | 0/467 | 1/233 |
| Event | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide |
|---|---|---|---|
| NauseaGastrointestinal disorders | 45/469 | 17/467 | 56/233 |
| DiarrhoeaGastrointestinal disorders | 42/469 | 20/467 | 21/233 |
| HeadacheNervous system disorders | 24/469 | 15/467 | 18/233 |
| Upper respiratory tract infectionInfections and infestations | 33/469 | 23/467 | 12/233 |
| NasopharyngitisInfections and infestations | 26/469 | 25/467 | 15/233 |
| VomitingGastrointestinal disorders | 15/469 | 7/467 | 15/233 |
| Age, Continuous(years) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Mean | 58.2 ± 9.5 | 58.3 ± 9.4 | 58.7 ± 8.7 | 58.4 ± 9.3 |
| Sex: Female, Male(Participants) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Female | 247 | 230 | 101 | 578 |
| Male | 222 | 237 | 133 | 592 |
| Race(Participants) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Caucasian | 417 | 421 | 216 | 1054 |
| Black | 33 | 33 | 12 | 78 |
| Asian/Oriental | 8 | 7 | 3 | 18 |
| Other | 11 | 6 | 3 | 20 |
| Ethnicity(Participants) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Hispanic | 85 | 87 | 51 | 223 |
| Not Hispanic | 384 | 380 | 183 | 947 |
| Second Oral Anti-diabetic Drug (OAD) Use(Participants) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Yes | 274 | 270 | 133 | 677 |
| No | 195 | 197 | 101 | 493 |
| Second OAD Use at Screening by Class(Participants) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Sulfonylurea | 259 | 249 | 123 | 631 |
| Glinide | 3 | 10 | 5 | 18 |
| Sodium-glucose co-transporter-2 inhibitor | 2 | 2 | 0 | 4 |
| Dipeptidyl peptidase-4 inhibitor | 12 | 11 | 5 | 28 |
| None | 193 | 195 | 101 | 489 |
| Body Mass Index (BMI)(kg/m^2) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Mean | 31.64 ± 4.4 | 31.66 ± 4.51 | 31.99 ± 4.39 | 31.72 ± 4.44 |
| Duration of Diabetes(years) | Insulin Glargine/Lixisenatide Fixed Ratio Combination | Insulin Glargine | Lixisenatide | Total |
|---|---|---|---|---|
| Mean | 8.89 ± 5.51 | 8.66 ± 5.59 | 8.89 ± 6.26 | 8.80 ± 5.69 |
3 further baseline measures are reported on the registry.
Showing the first 100 of 273 sites across 23 countries.
This study is completed, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.