Single Ascending Doses of ZP4207 Administered in HV and in T1D to Evaluate Safety, Tolerability PKs and PDs of ZP4207 Compared to a Comparator

NCT02367053 | Completed Phase 1

• 1 other identifier: ZP4207-14013
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is a randomized, double-blind First in Human trial to evaluate the safety and tolerability of ZP4207 in healthy volunteers (HV) and in insulin-induced hypoglycemic T1D (type 1 diabetes) subjects as compared to native glucagon. The trial includes two parts. Part 1 includes dose escalation of ZP4207 in cohorts of 8 subjects. In each cohort, subjects will be randomized 3:1 to receive either a single ascending dose of ZP4207 (6 subjects) or a single fixed dose (SD) of native glucagon (2 subjects). The doses will be administered s.c. in 4-5 cohorts and i.m. in 3 cohorts. Part 2 includes two sequence groups of 10 hypoglycemic T1D subjects. The subjects will be treated with fixed single doses of ZP4207 and native glucagon s.c. in a sequential cross-over design in a randomized treatment order.

Conditions

Hypoglycemia

Outcome Measures

Primary Outcomes (6)

• Safety and Tolerability: Number of participants with adverse events

  28 days

• Safety and Tolerability: Changes or findings from baseline in clinical safety laboratory assessments

  28 days

• Safety and Tolerability: Changes or findings from baseline in physical examination

  28 days

• Safety and Tolerability: Changes or findings from baseline in vital signs

  28 days

• Safety and Tolerability: Changes or findings from baseline in ECG

  28 days

• Safety and Tolerability: Findings in local tolerability

  28 days

Secondary Outcomes (12)

• Pharmacokinetics (PK): Area under the curve (AUC) from time-point 0 until 300min

  5 hours

• Pharmacokinetics: maximum observed concentration of ZP4207 (Cmax)

  5 hours

• Pharmacokinetics: time to maximum observed concentration of ZP4207 (tmax)

  5 hours

• Pharmacokinetics: terminal elimination rate constant estimated during the terminal phase of ZP4207 (λz)

  5 hours

• Pharmacokinetics: the terminal plasma elimination half-life of ZP4207 (t½),

  5 hours

Study Arms (2)

ZP4207

EXPERIMENTAL

single dose of ZP4207 in ascending doses (s.c. and i.m.)

Drug: ZP4207

native glucagon

ACTIVE COMPARATOR

single fixed dose of glucagon

Drug: Glucagon

Interventions

ZP4207 DRUG

ZP4207

Glucagon DRUG

native glucagon

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• Male subjects which are healthy for part 1; for part 2 male subjects with T1D
• Age between 18 and 50 years, both inclusive.
• Body weight between 70 and 90 kg, both inclusive.
• Subjects must be in good health according to age (medical history, physical examination, vital signs, ECG, lab assessments), as judged by the investigator
• A subject who is surgically sterilized or must be willing to refrain from sexual intercourse during the trial and until one month after completion of the trial or if sexually active, using condom and partner practices contraception during the trial and until one month after completion of the trial.
• For part 2, in addition:
• Male subjects with T1D for at least one year, as defined by the American Diabetes Association.
• Having been treated with insulin for T1D for at least 1 year.
• Stable disease with HbA1c \< 8.5 %.
• Stable insulin treatment during participation in trial and 3 month prior to the screening visit.

You may not qualify if:

• Known or suspected allergy to trial product(s) or related products.
• Previous participation (randomization) in this trial.
• Receipt of any investigational drug within 3 months prior to screening.
• A history or presence of cancer, diabetes (part 1 only), or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, hematological, dermatological, venereal, neurological, psychiatric diseases or other major diseases.
• Clinically significant illness within 4 weeks before screening, as judged by the investigator
• Carrier of Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies.
• Positive result of test for HIV antibodies.
• Any clinically significant abnormal hematology,biochemistry or urinalysis screening tests, as judged by the Investigator.
• Clinically significant abnormal ECG at screening as evaluated by Investigator.
• Donation of blood or plasma in the past month, or in excess of 500 ml within 12 weeks prior to screening.
• A significant history of alcoholism or drug/chemical abuse, or who has a positive result in the urine drug screen, or who consumes more than 28 units of alcohol per week (one unit of alcohol equals about 250 ml of beer, 1 glass of wine, or 20 ml of spirits).
• Habitual smoking, i.e., daily smoking or more than 7 cigarettes/week within the last 3 months prior to screening. Subjects have to accept refraining from smoking while at the clinical site.
• Subjects with mental incapacity or language barriers which preclude adequate understanding or cooperation, who are unwilling to participate in the trial, or who in the opinion of the Investigator should not participate in the trial.
• Surgery or trauma with significant blood loss within the last 2 months prior to screening.
• Any condition interfering with trial participation or evaluation or that may be hazardous to the subject.

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (1)

Profil GmbH

Neuss, 41460, Germany

Location

MeSH Terms

Conditions

Hypoglycemia

Interventions

Glucagon

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Thomas Jax, MD/PhD

  Profil GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 20, 2015
• Study Start: December 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: January 22, 2016

Record last verified: 2016-01

Locations

DE (1)