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A Trial to Assess the Efficacy and Safety of M1 Pram P037 Prandial Insulin in Subjects With Type 1 Diabetes (T1DM)

Phase 2
Completed
Conditions
Type 1 Diabetes Mellitus
Interventions
Drug: M1 Pram P037
Registration Number
NCT04816890
Lead Sponsor
Adocia
Brief Summary

In this trial, the treatment of subjects with type 1 diabetes with M1 Pram P037 as co-formulation of pramlintide and A21G human insulin analogue product will be compared with a current standard treatment, insulin lispro. During a four months treatment period doses in both treatment arms may be adjusted and optimised under outpatient conditions to allow a meaningful comparison of both treatments with respect to their effects on body weight, achievable glycaemic control, safety and tolerability, treatment satisfaction and well-being.

Detailed Description

After a run in period in case of basal insulin switch or Continuous Glucose Monitoring (CGM) initiation, eligible subjects will enter a 3 weeks baseline recording period.

Subjects will then be randomized to either M1 Pram P037 treatment or active comparator treatment (insulin lispro). Both investigator and enrolled subjects will be unblinded to treatment. Study participants will use CGM until follow-up visit.

Treatment period will last 16 weeks. Throughout the 4-month treatment period, basal insulin and investigational products administration will be individually adjusted. Treatment Satisfaction Questionnaire and WHO-5 well-being index will be completed by subjects at day 0 and after 2 months (Visit 9) and 4 months (Visit 11) of treatment.

A safety follow-up visit, 7 to 14 days after the last administration of IMP, will mark the end of the clinical trial for the subjects.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Signed and dated informed consent obtained before any trial-related activities. Trial-related activities are any procedures that would not have been done during normal management of the subject.
  • Subjects with type 1 diabetes mellitus.
  • Body Mass Index (BMI) between 25.0 and 35.0 kg/m^2, both inclusive.
  • HbA1c between 7.0 % and 9.5 %, both inclusive.
  • Diabetes duration of at least 12 months.
  • Using a multiple dosing insulin therapy (MDI) with a basal insulin and a rapid-acting insulin at at least two meals per day.
  • Using any CGM or Flash Glucose Monitoring (FGM) for at least 1 month or willing to use CGM during the trial.
Exclusion Criteria
  • Known or suspected hypersensitivity to IMPs or any of the excipients or to any component of the IMP formulation.
  • Type 2 diabetes mellitus.
  • Receipt of any medicinal product in clinical development within 3 months or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomisation in this trial.
  • History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
  • Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator.
  • Clinically significant abnormal screening laboratory tests, as judged by the Investigator.
  • Systolic blood pressure < 90 mmHg or >139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 mmHg. One repeat test (on a different day, if necessary) will be acceptable in case of suspected white-coat hypertension.
  • Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator.
  • Proliferative retinopathy or maculopathy as judged by the Investigator based on a recent (<1.5 years) ophthalmologic examination.
  • Severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
  • More than one episode of severe hypoglycaemia with seizure, coma or requiring assistance of another person during the past 6 months.
  • Hypoglycaemic unawareness as judged by the Investigator.
  • Hospitalisation for diabetic ketoacidosis during the previous 6 months.
  • Presence of clinically significant gastrointestinal symptoms (e.g., nausea, vomiting, heartburn or diarrhea), as judged by the Investigator.
  • Confirmed diagnosis of gastroparesis or requiring the use of drugs that alter gastrointestinal motility.
  • Unusual meal habits and special diet requirements that could constitute a risk for the subject when participating in the trial or interfere with the interpretation of data.
  • Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists within 4 weeks prior to screening.
  • Use of systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) within 2 months prior to screening.
  • Use or planned use of drugs that promote weight loss (e.g. liraglutide, semaglutide, orlistat, lorcaserin, phentermine) within 2 months prior to screening.
  • If female, pregnancy or breast-feeding.
  • Women of childbearing potential who are not using a highly effective contraceptive method.
  • The Investigator considers a subject as unsuitable for inclusion in the study for any other reason.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
M1 Pram P037M1 Pram P037Multi daily administration of M1 Pram P037 by subcutaneous injection
Insulin lisproInsulin lisproMulti daily administration of insulin lispro (Humalog®) by subcutaneous injection
Primary Outcome Measures
NameTimeMethod
Body weight change from baseline to week 16 of treatmentFrom week 0 to week 16

Change in body weight after 16 weeks of treatment

Secondary Outcome Measures
NameTimeMethod
MeanG_24hFrom week 0 to week 16

Average glucose over 24h change from baseline to week 16 of treatment

HbA1cFrom week 0 to week 16

HbA1c change from baseline to week 16 of treatment

TIR [70-140] mg/dL.From week 0 to week 16

Time In Range \[70-140\] mg/dL change from baseline to week 16 of treatment as measured by CGM.

%TIR [70-180] mg/dL.From week 0 to week 16

Percentage of Time In Range \[70-180\] mg/dL change from baseline to week 16 of treatment as measured by CGM.

%TIR [70-140] mg/dL.From week 0 to week 16

Percentage of Time In Range \[70-140\] mg/dL change from baseline to week 16 of treatment as measured by CGM.

CVG_24hFrom week 0 to week 16

Coefficient Of Variation of glucose over 24h change from baseline to week 16 of treatment.

SDG_24hFrom week 0 to week 16

Standard Deviation of all glucose values over 24h change from baseline to week 16 of treatment

Total Insulin dosesFrom week 0 to week 16

Change from baseline of total insulin doses

Number of Adverse EventsFrom week 0 to week 16

Number of Adverse Events observed during the treatment period

Duration of Adverse EventsFrom week 0 to week 16

Duration of Adverse Events observed during the treatment period

TIR [70-180] mg/dL.From week 0 to week 16

Time In Range \[70-180\] mg/dL change from baseline to week 16 of treatment as measured by CGM.

DistG_24hFrom week 0 to week 16

Distance travelled over 24h change from baseline to week 16 of treatment

Hypoglycaemic episodesFrom week 0 to week 16

Number of Hypoglycemic episodes during the 16 weeks treatment period

Prandial Insulin dosesFrom week 0 to week 16

Change from baseline of prandial (per meal), insulin doses

Basal Insulin dosesFrom week 0 to week 16

Change from baseline of basal insulin doses

Trial Locations

Locations (2)

Profil Mainz GmbH & Co

🇩🇪

Mainz, Germany

Profil Institut für Stoffwechselforschung GmbH

🇩🇪

Neuss, Germany

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