Phase 4 Study to Evaluate Treatment Optimization With Once-daily Insulin Glargine 300 U/mL (TOP1)

A 28-week, Prospective, Single-arm, Phase 4 Study to Evaluate Treatment Optimization With Once-daily Insulin Glargine 300 U/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

Primary Objective:

To evaluate the efficacy of switching treatment from twice-daily basal insulin to once-daily insulin glargine (U300) as part of basal bolus regime in terms of glycated hemoglobin improvement (reduction by at least 0.3%), in uncontrolled type 1 diabetes mellitus patients.

Secondary Objectives:

• To evaluate other efficacy parameters in terms of glycemic control as well as safety including hypoglycemia events, weight changes, and adverse events.
• To evaluate the effect of insulin glargine (U300) on diabetes treatment satisfaction and fear of hypoglycemia as well as patient's satisfaction regarding the number of daily injections.

Study Overview

• Status: Completed
• Conditions: Type I Diabetes Mellitus
• Intervention / Treatment: Drug: INSULIN GLARGINE (U300)

Detailed Description

The estimated average study duration is 29 weeks, including run-in period of 4 weeks; treatment period of 24 weeks, and follow-up period of 1 week.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Campinas, Brazil, 13092-132
    • Investigational Site Number 076013
  • Curitiba, Brazil, 80030-110
    • Investigational Site Number 076016
  • Curitiba, Brazil, 80810-140
    • Investigational Site Number 076007
  • Fortaleza, Brazil
    • Investigational Site Number 076005
  • Goiânia, Brazil, 74175-100
    • Investigational Site Number 076002
  • Porto Alegre, Brazil, 91350-250
    • Investigational Site Number 076004
  • Ribeirão Preto, Brazil, 14049900
    • Investigational Site Number 076011
  • SãO Paulo, Brazil
    • Investigational Site Number 076001
  • São José dos Campos, Brazil, 12243-280
    • Investigational Site Number 076006
  • São Paulo, Brazil, 04022-001
    • Investigational Site Number 076015
  • São Paulo, Brazil, 05403-000
    • Investigational Site Number 076012

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Male or Female.
• Age ≥ 18 years.
• With Type 1 diabetes mellitus.
• Being treated twice-daily with any basal insulin in combination with prandial rapid-acting insulin analogue for at least one year.
• Have an glycated hemoglobin (HbA1c) measurement of 7.5% - 10.0% at study entry.
• Patients who have signed an Informed Consent Form.

Exclusion criteria:

• Type 2 diabetes mellitus.
• Known hypoglycemia unawareness
• Repeated episodes of severe hypoglycemia or diabetes ketoacidosis within the last 12 months.
• End-stage renal failure or being on hemodialysis.
• Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening or baseline, or any major systemic disease resulting in short life expectancy that in the opinion of the Investigator would restrict or limit the patient's successful participation for the duration of the study.
• Known hypersensitivity / intolerance to insulin glargine or any of its excipients.
• Patients treated with glucagon like peptide agonists.
• Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 90 days prior to the time of screening.
• Pregnant or lactating women.
• Women of childbearing potential with no effective contraceptive method.
• Participation in another clinical trial.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin glargine (U300); Self-administered subcutaneously once daily in the morning, at the same time.The initial dose for patients switching from insulin glargine is 80% of the total daily dose of basal insulin agent that was discontinued. Thereafter, insulin glargine (U300) will follow a titration algorithm for dose adjustment.	Drug: INSULIN GLARGINE (U300); Pharmaceutical form: Solution for Injection Route of administration: Subcutaneous injection; Other Names: Toujeo, HOE901

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in HbA1c	Mean change in glycated hemoglobin (HbA1c) from baseline to Week 24 (%)	From baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in HbA1c	Mean HbA1c change from baseline to Week 12	From baseline to Week 12
Mean change in fasting plasma glucose (FPG)	Mean change in FPG from baseline to Week 12 and Week 24	From baseline to Week 12 and Week 24
Mean change in fasting SMBG	Mean change in fasting self-monitored blood glucose (SMBG) from baseline to Week 12 and Week 24	From baseline to Week 12 and Week 24
Mean change in 8-point SMBG	Mean change in 8-point SMBG from baseline to Week 12 and Week 24	From baseline to Week 12 and Week 24
Proportion of patients achieving HbA1c target of <7.0%	Proportion of patients achieving HbA1c target of <7.0% at Week 12 and Week 24	At Weeks 12 and 24
Proportion of patients achieving HbA1c target of <7.0% without hypoglycemia event	Proportion of patients achieving HbA1c target of <7.0% without hypoglycemia event during the last 4 weeks of treatment	At Weeks 12 and 24
Proportion of patients achieving HbA1c improvement of at least 0.3% without nocturnal hypoglycemia	Proportion of patients achieving HbA1c improvement from baseline to week 24 of at least 0.3% without nocturnal hypoglycemia (documented <70 mg/dL) and/or severe hypoglycemia (between 00.00 and 05:59 am SMBG) during the last 4 weeks of treatment	From baseline to Week 24
Proportion of patients with any improvement in HbA1c	Proportion of patients with any improvement in HbA1c from baseline to week 24 and decrease in occurrence of nocturnal hypoglycemia (nocturnal defined as time between 00.00 and 05:59 am) evaluated from baseline to Week 24	From baseline to Week 24
Proportion of patients with no deterioration in HbA1c	Proportion of patients with no deterioration in HbA1c from baseline to week 24 and decrease in occurrence of nocturnal hypoglycemia	From baseline to Week 24
Proportion of patients with no deterioration in HbA1c	Proportion of patients with no deterioration in HbA1c from baseline to week 24 and no increase in occurrence of nocturnal hypoglycemia	From baseline to Week 24
Adverse events (AEs)	Number of adverse events and serious adverse events	Up to 28 weeks
Mean change in body weight	Mean change in body weight from baseline to Weeks 12 and 24	From baseline to Week 12 and Week 24
Mean change in daily insulin doses	Insulin glargine (U300) dose: Mean change in daily insulin doses (basal, prandial, total) from baseline to Week 24	From baseline to Week 24
Number of patients experiencing hypoglycemia		Up to 28 weeks
Proportion of patients experiencing hypoglycemia		Up to 28 weeks
Number of hypoglycemic events per patient-year		Up to 28 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2018
• Primary Completion (Actual): February 4, 2019
• Study Completion (Actual): February 4, 2019

Study Registration Dates

• First Submitted: January 15, 2018
• First Submitted That Met QC Criteria: January 19, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine
• Other Study ID Numbers: GLARGL08200; U1111-1186-2485 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No