Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39361   clinical trials with a EudraCT protocol, of which   6446   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    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

    Summary
    EudraCT number
    2015-001186-46
    Trial protocol
    BE  
    Global end of trial date
    10 May 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    09 May 2019
    First version publication date
    09 May 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    GLARGL07699
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    STUDY NAME: OPTIMIZE
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement , Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement , Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Aug 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 May 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    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.
    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.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Dec 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 48
    Country: Number of subjects enrolled
    Canada: 46
    Worldwide total number of subjects
    94
    EEA total number of subjects
    48
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    82
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Subjects were involved in the study from 17 December 2015 to 10 May 2018 at 25 centers in Belgium and Canada.

    Pre-assignment
    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.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    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
    Investigational medicinal product code
    HOE901-U300
    Other name
    Toujeo®
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1.5 mL, subcutaneous, self administered using a prefilled disposable SoloSTAR® pen once daily in the morning for 24 weeks.

    Number of subjects in period 1
    HOE901-U300
    Started
    94
    Completed
    94

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    HOE901-U300
    Reporting group description
    Subjects received insulin glargine HOE901-300 IU/mL, once daily, subcutaneous (SC) injection for 24 weeks.

    Reporting group values
    HOE901-U300 Total
    Number of subjects
    94 94
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    49.4 ± 13.1 -
    Gender categorical
    Units: Subjects
        Female
    50 50
        Male
    44 44
    Body mass index (BMI)
    Units: kg/m^2
        arithmetic mean (standard deviation)
    27.8 ± 4.7 -
    Duration of disease
    Units: years
        arithmetic mean (standard deviation)
    27.3 ± 12.9 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    HOE901-U300
    Reporting group description
    Subjects received insulin glargine HOE901-300 IU/mL, once daily, subcutaneous (SC) injection for 24 weeks.

    Primary: Change From Baseline in HbA1c at Week 24

    Close Top of page
    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.
    End point type
    Primary
    End point timeframe
    Baseline, Week 24
    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.
    End point values
    HOE901-U300
    Number of subjects analysed
    94
    Units: Percentage of HbA1c
        arithmetic mean (confidence interval 95%)
    0.2745 (0.1507 to 0.3982)
    No statistical analyses for this end point

    Secondary: Change From Baseline in HbA1c to Week 12

    Close Top of page
    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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    HOE901-U300
    Number of subjects analysed
    90
    Units: Percentage of HbA1c
        arithmetic mean (confidence interval 95%)
    0.4011 (0.2862 to 0.5160)
    No statistical analyses for this end point

    Secondary: Evolution of Fasting Plasma Glucose (FPG)

    Close Top of page
    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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and Week 24
    End point values
    HOE901-U300
    Number of subjects analysed
    93
    Units: mg/dL
    arithmetic mean (standard error)
        Baseline (n= 93)
    217.783 ± 91.6753
        Week 12 (n = 86)
    191.748 ± 68.6914
        Week 24 (n= 85)
    208.132 ± 82.3453
    No statistical analyses for this end point

    Secondary: Evolution in Fasting Self-Monitored Plasma Glucose (SMBG)

    Close Top of page
    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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and Week 24
    End point values
    HOE901-U300
    Number of subjects analysed
    88
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n= 88)
    198.454 ± 90.0085
        Week 12 (n= 84)
    172.826 ± 86.7930
        Week 24 (n= 83)
    181.786 ± 79.2007
    No statistical analyses for this end point

    Secondary: Evolution of SMBG Between 3 AM And Bedtime at Baseline and Week 24

    Close Top of page
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24
    End point values
    HOE901-U300
    Number of subjects analysed
    94
    Units: mg/dL
    arithmetic mean (standard deviation)
        Pre-breakfast: Baseline (n= 88)
    198.454 ± 90.0085
        Pre-breakfast: Week 24 (n= 83)
    181.786 ± 79.2007
    Attachments
    Mean SMBG (mg/dL) ± SE
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieved HbA1c target of <7.0% at Week 12 and Week 24

    Close Top of page
    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.
    End point type
    Secondary
    End point timeframe
    Week 12 and Week 24
    End point values
    HOE901-U300
    Number of subjects analysed
    94
    Units: Percentage of Subjects
    number (not applicable)
        Week 12
    0
        Week 24
    0
    No statistical analyses for this end point

    Secondary: 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

    Close Top of page
    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.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 24
    End point values
    HOE901-U300
    Number of subjects analysed
    92
    Units: Percentage of subjects
        number (not applicable)
    5.4
    No statistical analyses for this end point

    Secondary: Number of Hypoglycemic Events Per Patient Year During Run-in Period and Last 4 weeks of Treatment

    Close Top of page
    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.
    End point type
    Secondary
    End point timeframe
    Run-in period (Week -4 to Week 0), last 4 weeks of treatment (Week 20 to 24)
    End point values
    HOE901-U300
    Number of subjects analysed
    94
    Units: Events per patient-year
    arithmetic mean (standard deviation)
        Nocturnal: Run-in period (n= 70)
    16.40 ± 20.38
        Nocturnal:Last 4 weeks of treatment (n= 70)
    13.66 ± 23.79
        Severe: Run-in period (n= 69)
    1.04 ± 3.42
        Severe: Last 4 weeks of treatment (n= 69)
    1.95 ± 7.52
        Confirmed (<=70 mg/dL):Run-in period (n= 69)
    93.17 ± 67.22
        Confirmed<=70 mg/dL Last 4 weeks of treatment n=69
    97.83 ± 75.45
        Confirmed (<54mg/dL):Run-in period (n= 70)
    33.40 ± 31.04
        Confirmed<54mg/dL: Last 4 weeks of treatment n=70
    37.14 ± 39.85
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    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.
    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.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    HOE901-U300
    Reporting group description
    Subjects received insulin glargine HOE901-300 IU/mL, once daily, SC injection for 24 weeks.

    Serious adverse events
    HOE901-U300
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 94 (4.26%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Thrombosis
         subjects affected / exposed
    1 / 94 (1.06%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine Leiomyoma
         subjects affected / exposed
    1 / 94 (1.06%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Hypoglycaemic Coma
         subjects affected / exposed
    1 / 94 (1.06%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    1 / 94 (1.06%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    HOE901-U300
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 94 (28.72%)
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 94 (5.32%)
         occurrences all number
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 94 (5.32%)
         occurrences all number
    5
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    6 / 94 (6.38%)
         occurrences all number
    8
    Vomiting
         subjects affected / exposed
    5 / 94 (5.32%)
         occurrences all number
    7
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    15 / 94 (15.96%)
         occurrences all number
    17

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    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.
    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.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA