A First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM12460A (HM12460A)

Study Design:

Part 1.Randomized, double-blind, placebo-controlled, escalating single-dose design with Healthy volunteers Part 2.Open , sequential, two-period, single dose study with type 1 diabetes Part 3.Open, sequential, two-period, single dose study with type 2 diabetes

Study Overview

• Status: Completed
• Conditions: Healthy; Type 2 Diabetes Mellitus; Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: HM12460A; Drug: Placebo

Detailed Description

The principle objectives of this study are to assess safety and tolerability and to explore pharmacokinetic(PK) and pharmacodynamic(PD) parameters of a single dose of a novel very-long acting insulin formulation (HM12460A) in comparison to a single dose of human Neutral Protamine Hagedorn (NPH) in healthy volunteers (part 1), subjects with type 1 diabetes (part 2) and in subjects with type 2 diabetes (part 3).

The study will incorporate adaptive elements to provide both PK and PD data. The dose of HM12460A to be administered to the subjects with type 1 diabetes and type 2 diabetes will be guided by PK data from part 1 of the study; the PD assessment of HM12460A in subjects with diabetes will also be informed by knowledge of PK gained from the healthy volunteer study.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Hanmi pharma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy subjects

• Age ≥18 and ≤70 years
• Non-obese; body mass index between 18.0 and 30.0 kg/m2 inclusive.
• Considered generally healthy upon completion of medical history, physical examination and biochemical investigations as judged by the Investigator.
• Non-smoker, or light smoker, defined as <15 cigarettes/day and able to abstain from smoking during confinement period.
• Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal for >12 months. Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, the subject must be using an acceptable contraceptive method during and for during a period of 60 days after the last dose of Study Drug.
• Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject).

Exclusion Criteria:

• Previous participation in this trial or other clinical trials within the last 3 months.
• Clinically significant abnormal hematology or biochemistry screening tests, as judged by the Investigator. In particular, healthy subjects with liver enzymes above the upper limit of the normal range and subjects with diabetes who have elevated liver enzymes (AST or ALT >2 times the upper limit of normal) or impaired renal function (elevated serum creatinine values above the upper limit of normal) will be excluded.
• History of any illness that, in the opinion of the Investigator, might confound the results of the trial or pose risk in administering the trial drug to the subject. In particular, subjects with significant cardiovascular disease, anemia (hemoglobin below the lower limit of normal) or hemoglobinopathy will not be allowed to enter the trial.
• Clinically significant abnormal ECG at screening, as judged by the Investigator.
• History of alcohol abuse.
• Any positive reaction of drugs of abuse.
• Hepatitis B or C or HIV positive.
• Use of prescription drugs within 3 weeks preceding the first dosing of insulin, except for medications deemed acceptable per protocol specific list of concomitant medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort S1; HM12460A Dose 1 (1.2 nmol/kg) or placebo	Drug: HM12460A; Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A; Other Names: LAPS-Insulin; Drug: Placebo; Singe dose SC administration of Placebo
Experimental: Cohort S2; HM12460A Dose 2 (2.4 nmol/kg) or Placebo	Drug: HM12460A; Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A; Other Names: LAPS-Insulin; Drug: Placebo; Singe dose SC administration of Placebo
Experimental: Cohort S3; HM12460A Dose 3 (4.8 nmol/kg) or Placebo	Drug: HM12460A; Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A; Other Names: LAPS-Insulin; Drug: Placebo; Singe dose SC administration of Placebo
Experimental: Cohort S4; HM12460A Dose 4 (9.6 nmol/kg) or Placebo	Drug: HM12460A; Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A; Other Names: LAPS-Insulin; Drug: Placebo; Singe dose SC administration of Placebo
Experimental: Cohort S5; HM12460A Dose 5 (14.4 nmol/kg) or Placebo	Drug: HM12460A; Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A; Other Names: LAPS-Insulin; Drug: Placebo; Singe dose SC administration of Placebo
Experimental: Cohort S6; HM12460A Dose 6 (19.2 nmol/kg) or Placebo	Drug: HM12460A; Single dose SC administration ranging from 1.2 nmol/kg to 19.2 nmol/kg of HM12460A; Other Names: LAPS-Insulin; Drug: Placebo; Singe dose SC administration of Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of treatment emergent adverse events	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration(Cmax) of HM12460A following a single dose in Parts 1-3	PK properties of HM12460A following a single dose in Parts 1-3 will be assessed in plasma using a validated assay	one year

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 5, 2012
• First Submitted That Met QC Criteria: November 7, 2012
• First Posted (Estimate): November 12, 2012

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: November 1, 2017

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 2; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: HM-INS-101