Clinical Trial Results:
A 28-Week, Prospective, Single-Arm, Open Label Phase 4 Study to Evaluate Treatment Optimization With Once-Daily Insulin Glargine HOE901-300 IU/Ml In Combination With Prandial Rapid-Acting Insulin Analogue In Patients With Type 1 Diabetes Previously Uncontrolled on Twice Daily Basal Insulin as Part of Basal-Bolus Therapy
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Summary
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EudraCT number |
2015-001186-46 |
Trial protocol |
BE |
Global end of trial date |
10 May 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
09 May 2019
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First version publication date |
09 May 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GLARGL07699
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Additional study identifiers
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ISRCTN number |
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US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
STUDY NAME: OPTIMIZE | ||
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Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement , Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement , Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Aug 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 May 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of optimizing treatment from twice-daily (BID) basal to once-daily (OD) insulin glargine HOE901-300 IU/mL as part of basal bolus regime in terms of improving Hemoglobin A1c (HbA1c) by at least 0.3% in uncontrolled type 1 diabetes mellitus subjects.
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject was participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
17 Dec 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 48
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Country: Number of subjects enrolled |
Canada: 46
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Worldwide total number of subjects |
94
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EEA total number of subjects |
48
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
82
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were involved in the study from 17 December 2015 to 10 May 2018 at 25 centers in Belgium and Canada. | ||||||
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Pre-assignment
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Screening details |
A total of 130 subjects were screened, of which 36 subjects had screening failure. After a 4 week run-in period, 94 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and switched from their basal insulin treatment to HOE901-U300. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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HOE901-U300 | ||||||
Arm description |
Subjects received insulin glargine HOE901-300 IU/mL, once daily, subcutaneous (SC) injection for 24 weeks. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Insulin glargine
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Investigational medicinal product code |
HOE901-U300
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Other name |
Toujeo®
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
1.5 mL, subcutaneous, self administered using a prefilled disposable SoloSTAR® pen once daily in the morning for 24 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
HOE901-U300
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Reporting group description |
Subjects received insulin glargine HOE901-300 IU/mL, once daily, subcutaneous (SC) injection for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
HOE901-U300
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Reporting group description |
Subjects received insulin glargine HOE901-300 IU/mL, once daily, subcutaneous (SC) injection for 24 weeks. | ||
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End point title |
Change From Baseline in HbA1c at Week 24 [1] | ||||||||
End point description |
Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). Baseline was defined as the last available value prior to the first dose of investigational medicinal product (IMP). The analysis was performed on intent-to-treat (ITT) population, which included all evaluable subjects for the 24 week treatment period, regardless of whether the IMP was taken or not and whatever the duration of their follow-up period.
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End point type |
Primary
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End point timeframe |
Baseline, Week 24
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint contains single arm, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in HbA1c to Week 12 | ||||||||
End point description |
Change in HbA1c was calculated by subtracting baseline value from Week 24 value. The analysis was performed on ITT population. Here, ‘number of subjects analysed’ = subjects with available data for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Evolution of Fasting Plasma Glucose (FPG) | ||||||||||||||
End point description |
The analysis was performed on ITT population. Here, 'number of subjects analysed' = total number of subjects with available data for this endpoint and 'n' = number of subjects with available data for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12 and Week 24
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Evolution in Fasting Self-Monitored Plasma Glucose (SMBG) | ||||||||||||||
End point description |
The analysis was performed on ITT population. Here, 'number of subjects analysed' = total number of subjects with available data for this endpoint and 'n' = number of subjects with available data for specified categories.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12 and Week 24
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Evolution of SMBG Between 3 AM And Bedtime at Baseline and Week 24 | ||||||||||||
End point description |
SMBG profiles measured at the following 8 points: pre-breakfast, 2-hour post-breakfast, pre-lunch, 2-hour post-lunch, pre-dinner, 2-hour post-dinner, bedtime, and at 3:00 am. Subjects were requested to perform 8-point SMBG profiles over a single 24-hour period on one day during the week before baseline, Week 4, Week 8, Week 12, and Week 24. On days when 8-point profiles were done, 03.00 AM was considered as the first point of measurement, i.e. “night” time point. The analysis was performed on ITT population. Here, 'n' = number of subjects with available data for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24
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Attachments |
Mean SMBG (mg/dL) ± SE |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Achieved HbA1c target of <7.0% at Week 12 and Week 24 | ||||||||||||
End point description |
Percentage of subjects achieving HbA1c target of <7.0% at Week 12 and Week 24 were calculated by 95% Clopper-Pearson confidence intervals (CIs). The analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Week 12 and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Achieving HbA1c Improvement From Baseline to Week 24 of At Least 0.3% Without Nocturnal Hypoglycemia (Documented <= 70 mg/dL or 3.9 mmol/L) and/or Severe Confirmed Hypoglycemia | ||||||||
End point description |
Severe hypoglycemia was an event in which the subject required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed by plasma glucose =<3.9 mmol/L (=<70 mg/dL). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time). Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of =<3.9 mmol/L (=<70 mg/dL). Analysis was performed on ITT population. Here, number of subjects analysed=subjects with available data for this end point.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Hypoglycemic Events Per Patient Year During Run-in Period and Last 4 weeks of Treatment | ||||||||||||||||||||||||
End point description |
Number of hypoglycemia per patient-year was computed per patient as: 365.25 x (number of episodes of hypoglycemia / number of days exposed) and summarized by observation period (i.e., 4-week run-in period, last 4 weeks on-treatment period). Run-in period was defined as the time between the date of the informed consent and the first insulin glargine HOE901-300 IU/mL injection. Last 4-weeks on-treatment period defined by the last 4-weeks preceding the last injection of insulin glargine HOE901-300 IU/mL. Here, 'n' = number of subjects with available data for specified time points.
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End point type |
Secondary
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End point timeframe |
Run-in period (Week -4 to Week 0), last 4 weeks of treatment (Week 20 to 24)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All AEs were collected from signature of the informed consent form up to the last visit (Week 25) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported AEs are TEAEs that is AEs that developed/worsened from first study drug intake up to Week 25. Analysis was performed on safety population which included subjects who were exposed to at least one dose of IMP, regardless of the amount of treatment administered.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
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Reporting groups
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Reporting group title |
HOE901-U300
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Reporting group description |
Subjects received insulin glargine HOE901-300 IU/mL, once daily, SC injection for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Sep 2016 |
Following amendments were added: -Sanofi-aventis Canada was added to Sanofi Belgium to ensure sufficient subjects recruitment.
-Sample size was reduced from 119 to 102, to accept a global power of 85% instead of 90%.
-Estimated centers number was increased to 30. Specialty and experience of the investigators (endocrinologists) was removed.
-Recommended starting dose of insulin glargine HOE901-300 IU/mL was amended.
-Dose adjustment was amended to modify proposed dose by adding more than 1U if value of median fasting SMBG from the last 3 days was >130 mg/dL.
-Dose adjustment was amended to harmonize with Table 1 of protocol.
-A “x” was added at Visit V0 in the flow chart to measure and record the vital signs (BP, weight and heart rate). The sentence “An HbA1c value from just before the run-in period should be available” was removed.
-Pen needle length was clarified to allow another length of needle than 5 mm.
-Canada and Belgium storage conditions text wash modified according the country regulations.
-The text was modified to allow nurses to perform the tracking and reconciliation of the NIMP.
-The HbA1c testing “National Glycohemoglobin Standardization Program” (NGSP) method was allowed.
-Subjects were allowed to use their blood glucose system with the exception of five 8-point SMBG analysis.
-Laboratory tests for inclusion & exclusion criterias were allowed to perform within 72 hours before visits 0 & 1.
-Pregnancy check by serum or urine pregnancy testing was added.
-Obligation of sponsor to be reported in an expedited manner was added and was applicable only for Canada.
-Record retention was adapted to different retention times for Belgium (20 years) & Canada (25 years) after completion or discontinuation of the clinical trial. |
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04 Jul 2017 |
- The total expected number of subjects was fixed to 90 and the required power to 80%.
- An interim analysis was performed to assess the Belgian data.
- A partial database lock was done after the last subject in Belgium had completed the last visit.
- The planned database lock date was fixed 3 months after last patient last visit.
- The sentence: “Once in use, replace pre-filled pen if not completely used within the period allowed by the regulating authorities applicable in the country (4 weeks in Belgium; 42 days in Canada)” was replaced by “Once in use, replace pre-filled pen if not completely used within the period allowed by the regulating authorities applicable in the country”.
- The sentence: “All hypoglycemia episodes will be documented on the “hypoglycemia specific form” and on an AE form in the e-CRF. This includes all symptomatic hypoglycemia events and asymptomatic hypoglycemia. A SAE complementary form in the e-CRF will be completed in addition to the AE form “hypoglycemia specific form” for Hypoglycemia events fulfilling the criteria of an SAE” was replaced by “All hypoglycemia episodes will be documented on the “hypoglycemia specific form” in the e-CRF. This included all symptomatic hypoglycemia events and asymptomatic hypoglycemia. A serious adverse event (SAE) complementary form in the e-CRF would be completed in addition to the “hypoglycemia specific form” for Hypoglycemia events fulfilling the criteria of an SAE.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
