A dose escalating open label study in Type 1 diabetic subjects, to assess the pharmacodynamics activity of transbuccal human recombinant insulin compared to subcutaneous human insulin.
Midatech Pharma Pty Ltd:
12 participants
Jul 28, 2015
Interventional
Conditions
Summary
This study is a single site, open label, cross-over, eight arm study to compare the effect of treating subjects with type 1 diabetes mellitus (T1DM) using a film (via the inner cheek) to deliver recombinant human insulin and standard subcutaneous insulin administration. Participants will receive three (3) comparator arm treatments versus five (5) investigational product arms over approximately six (6) month study participation period. Twelve (12) patients will be recruited for the study, with the possibility of eighteen (18) patients being required.
Eligibility
Inclusion Criteria12
- Age between 18 and 55 years
- Body mass index (BMI) equal to or great than 18 kg/m2 and equal to or less than 30 kg/m2.
- Diagnosis of T1DM made at least 2 years prior to study screening day, on an insulin pump or multiple insulin injections daily.
- HbA1c at screening less than 10 percent.
- Subject understands the study requirements and the treatment procedures, and is willing to comply with all specified follow-up evaluations, and provides written Informed Consent before any study-specific tests or procedures are performed.
- Subject is C- peptide negative (less than 0.2 nmol/L) on screening.
- Female subjects must be 1 year post-menopause, surgically sterile, or if sexually active, using an acceptable method of contraception to prevent pregnancy for the duration of the study (from the time they consent until 4 weeks after the last dose of the IP). Post menopause is defined as complete cessation of menstruation for 12 months.
- Women of childbearing potential must have a negative urine pregnancy test at screening and at check-in (Day-1). Female subjects must not become pregnant during the study and so must be confirmed as surgically sterile (based on documented hysterectomy or bilateral tubal ligation),
- Male partner sterilization (vasectomy with documentation of azoospermia), sexually inactive by abstinence or use following contraceptive methods from the time of the first dose of study treatment until at least 4 weeks after the final dose of study treatment.
- Abstinence: Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Complete abstinence from sexual intercourse for 14 days prior to first dose of study treatment, through the dosing period, and for at least 4 weeks after the last dose of study treatment.
- Contraceptive Methods: Use of two of the following: Hormonal Contraceptives (oral, injectable, implant, patch, ring), Barrier Contraceptives (condom or diaphragm) or Intrauterine device.
- Male subjects, if sexually active, must agree to use condoms during intercourse for the duration of the study and for 3 months after the last dose of study treatment. Male subjects must not donate sperm for the duration of the study period and for 3 months after the last dose of study treatment.
Exclusion Criteria21
- History of drug or alcohol abuse in the opinion of the Investigator.
- History of severe or multiple allergies in the opinion of the Investigator.
- Treatment with any investigational drug/device within 1 month or 5 half-lives of the IP (whichever is longer) prior to screening.
- Progressive fatal disease.
- History of significant cardiovascular, respiratory, gastrointestinal, hepatic, neurological, psychiatric and/or hematological disease defined at the discretion of the Investigator.
- History or evidence of renal impairment of greater than Chronic Kidney Disease (CKD) stage 2.
- Pregnant or lactating woman.
- Lack of compliance or other similar reason that, according to Investigator, precludes satisfactory participation in the study.
- History of Coronary Artery Bypass Graft (CABG), Myocardial Infarction (MI), active Ischemic heart disease, or Class II or greater congestive heart failure.
- History of Cardiovascular Accident (CVA) or Transient Ischemic Accident (TIA).
- Hypertension (blood pressure greater than 140/90 mm Hg) at screening (BP may be repeated up to 2 additional times after five minute semi supine rest period with the lowest BP taken as the measurement).
- Low blood hemoglobin concentration equal to or less than 12 g/dL for female and equal to or less than 13 g/dL for male, at screening.
- Psychological incompetence, whereby subject is assessed as being unable to provide information, consent, or comply with study requirements and procedures in the opinion of the Investigator.
- Diminished skin integrity at the relevant injection sites in particular the abdomen.
- Involved in or planned to participate in other studies that may interfere in data collection in the opinion of the Investigator.
- Unstable blood glucose levels at the discretion of the Investigator.
- Daily insulin requirements greater than 80 IU
- Any significant secondary complications of diabetes including neuropathy, ketoacidosis, nephropathy, cardiovascular disease, stroke, and retinopathy as defined by the Investigator.
- Experienced more than one episode of severe hypoglycemia in past 6 months requiring hospital intervention
- Suffered more than one episode of Diabetic Ketoacidosis (DKA) in the past 6 months requiring hospital intervention.
- Any other reason that, in the opinion of the Investigator, the volunteer is unsuitable to participate
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Interventions
This study is an open label, eight arm crossover study in participants with T1DM, designed to evaluate the pharmacodynamics, pharmacokinetics, and safety of four doses of MSL-001 (the transbuccal human recombinant insulin intervention) compared to recombinant human insulin (Humulin). Transbuccal human recombinant insulin intervention is where the administration of the insulin intervention is by placing the film strips on the inner cheek. It consists of 10 subject visits: the screening visit (V0), eight treatment visits (V1-V8), and a safety follow up visit (V9). Between each treatment visit there is a 7-21 day window allowed for adequate washing out. At the screening visit (Day -28 to day -3) subjects will be informed about the study and sign the informed consent if they agree to participate. Participants will check in the evening prior to each treatment visit and undergo safety assessments prior to study drug treatment. At each treatment visit, a subject will receive a single dose of MSL-001 (the transbuccal human recombinant insulin intervention) or the comparator (subcutaneous insulin). By the end of the study, each subject will have received both formulations of MSL-001 (the transbuccal human recombinant insulin intervention) and the comparator drug. Therefore at each treatment visit, participants will receive one dose per visits of the treatments noted below. *Comparator Arms: Recombinant Human Insulin Subcutaneous (SC) dose 5IU Recombinant Human Insulin Subcutaneous (SC) dose 10IU Recombinant Human Insulin Subcutaneous (SC) dose 15IU *Film formulations A and Formulation B (the transbuccal human recombinant insulin intervention): Formulation A: 1 x 5IU film for 5IU dose (plus 3 placebo films) Formulation B: 1 x 5IU film for 5IU dose (plus 3 placebo films) Formulation A or Formulation B:1 x 15IU film for 15IU dose (plus 3 placebo films)** Formulation A or Formulation B: 4 x 5IU films for 20IU dose (no placebo films)** Formulation A or Formulation B: 4 x 15IU films for 60IU dose (no placebos films)** **Following dosing with the Formulation B 5IU dose, data from the the three 5IU formulations (subcutaneous 5IU, Formulation A 5IU film and Formulation B 5IU film) will be analysed to determine which film formulation will be utilised for the remainder of the study. Both formulations contain the same active product and the same excipients and are prepared essentially using the same process. However, the ingredient list for Formulation B includes hydropropylmethylcellulose and glycerin whereas the ingredient list for Formulation A was simplified and lacks hydropropylmethylcellulose and glycerin. **As noted above, the mode of administration of the film strips is by placing the film strips on the inner cheek. The duration of study participation for participants completing the study is up to 112 days. The estimated duration of the total study is approximately 6 months. The end of study is defined as the date of the last visit of the last particpant.
Locations(1)
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ACTRN12615000495527