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Single Doses of ZP4207 Adm. sc to Hypoglycemic TD1 pt. to Describe the PK and PD of ZP4207 as Comp. to Marketed Glucagon

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ClinicalTrials.gov Identifier: NCT02660008
Recruitment Status : Completed
First Posted : January 21, 2016
Last Update Posted : June 15, 2016
Sponsor:
Information provided by (Responsible Party):
Zealand Pharma

Brief Summary:
The trial is a single-centre, randomized, double-blind, parallel trial in Group 1 and cross-over trial in Groups 2-4 with single doses of ZP4207 administered s.c. to hypoglycemic Type 1 diabetic patients to evaluate the pharmacokinetics and pharmacodynamics of ZP4207 as compared to marketed glucagon.

Condition or disease Intervention/treatment Phase
Hypoglycemia Drug: ZP4207 Drug: GlucaGen Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Trial of Single Doses of ZP4207 Administered s.c. to Hypoglycemic Type 1 Diabetic Patients to Describe the Pharmacokinetics and Pharmacodynamics of ZP4207 as Compared to Marketed Glucagon
Study Start Date : January 2016
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia
Drug Information available for: Glucagon

Arm Intervention/treatment
Experimental: ZP4207
ZP4207 (peptide analogue of human glucagon) Planned doses: 0.1, 0.3, 0.6, 1.0 mg s.c.
Drug: ZP4207
Parallel trial in Group 1 and cross-over trial in Groups 2-4 with single doses of ZP4207 administered s.c. to hypoglycemic Type 1 diabetic patients
Other Name: analogue af human glucagon

Active Comparator: GlucaGen
GlucaGen (native glucagon) Planned doses: 0.5, 1.0 mg s.c.
Drug: GlucaGen
Parallel trial in Group 1 and cross-over trial in Groups 2-4 with single doses of GlucaGen administered s.c. to hypoglycemic Type 1 diabetic patients
Other Name: glucagon




Primary Outcome Measures :
  1. PD endpoint: Plasma glucose profiles 0-360 min above baseline (Area under the effect curve 0-360 min) [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3

  2. PD endpoint: Time to peak plasma glucose concentration (tmax) [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3

  3. PK endpoint: Plasma ZP4207 and glucagon profiles 0-360 min [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3

  4. PK endpoint: Peak plasma concentration (Cmax) [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3

  5. PK endpoint: Time to peak plasma concentration (tCmax) [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3


Secondary Outcome Measures :
  1. PD endpoints: Percentage of patients achieving a plasma glucose concentration ≥70 mg/dL within 30 minutes after treatment [ Time Frame: During visit 2 and 3 (0-30min) ]
    At visit 2 and 3

  2. PD endpoints: Time to plasma glucose concentration of ≥70 mg/dL [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3

  3. PD endpoints: Percentage of patients achieving a plasma glucose increase of ≥20 mg/dL within 30 minutes after treatment [ Time Frame: During visit 2 and 3 (0-30min) ]
    At visit 2 and 3,

  4. PD endpoints: Time to plasma glucose increase of ≥20 mg/dL [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3,

  5. PK endpoints: Baseline adjusted glucagon profiles 0-360 min [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3,

  6. PK endpoints: AUC0-inf for plasma ZP4207 concentration [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3, Area under the plasma curve from 0 to infinity

  7. Exploratory endpoint: Insulin concentrations [ Time Frame: During visit 2 and 3 (0-360min) ]
    At visit 2 and 3, insulin concentrations in serum

  8. Exploratory endpoint: Changes in hypoglycaemic symptom scores from 0-30 minutes [ Time Frame: During visit 2 and 3 (0-30min) ]
    At visit 2 and 3

  9. Safety and Tolerability: Number of participants with adverse events [ Time Frame: Through study completion (up to 63 days) ]
    Number of participants with adverse events

  10. Safety and Tolerability: Changes or findings from baseline in physical examination [ Time Frame: Through study completion (up to 63 days) ]

    An examination of the following body systems will be performed:

    • Head, ears, eyes, nose, throat (HEENT), incl. thyroid gland
    • Heart, lung, chest
    • Abdomen
    • Skin and mucosae
    • Musculoskeletal system
    • Nervous system
    • Lymph node
    • Other findings

  11. Safety and Tolerability: Changes or findings from baseline (normal ranges) in clinical safety laboratory parameters [ Time Frame: Through study completion (up to 63 days) ]
    Haematology biochemistry, and urinalysis

  12. Safety and Tolerability: Changes or findings from baseline in vital signs [ Time Frame: Through study completion (up to 63 days) ]
    systolic/diastolic blood pressure (mmHg) and heart rate (beats per minute), body temperature (°C), respiratory frequency (RF/min)

  13. Safety and Tolerability: Changes or findings from baseline in ECG [ Time Frame: Through study completion (up to 63 days) ]
    Heart rate, PQ, QRS, QT, QTcB

  14. Safety and Tolerability: Local tolerability of injection site [ Time Frame: Through study completion (up to 63 days) ]

    Findings in local tolerability by means of the following assessments.

    • spontaneous pain
    • pain on palpation
    • itching
    • redness
    • oedema
    • induration/infiltration
    • other

  15. Safety and Tolerability: Immunogenicity (Ant-Drug Antibody sampling) [ Time Frame: Through study completion (up to 63 days) ]
    Antidrug antibodies incidences



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 patient).
  2. Male and female patients with T1D for at least one year, as defined by the American Diabetes Association.
  3. Having been treated with insulin for T1D for at least 1 year.
  4. Stable disease with HbA1c < 8.5%.
  5. Expected stable insulin treatment during participation in trial and 3 month prior to the screening visit.
  6. Age between 18 and 50 years, both inclusive.
  7. Body weight between 60 and 90 kg, both inclusive.
  8. Patients in good health according to age (medical history, physical examination, vital signs, ECG, lab assessments), as judged by the Investigator.

Exclusion Criteria:

  1. Previously treated with ZP4207.
  2. Known or suspected allergy to trial product(s) or related products.
  3. Previous participation (randomization) in this trial.
  4. Receipt of any investigational drug within 3 months prior to screening.
  5. A history or presence of cancer, or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, hematological, dermatological, venereal, neurological, psychiatric diseases, or other major diseases.
  6. Clinically significant illness within 4 weeks before screening, as judged by the Investigator.
  7. History of, or positive results to the screening test for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies
  8. Positive result of test for HIV antibodies.
  9. Any clinically significant abnormal hematology, biochemistry or urinalysis screening tests, as judged by the Investigator.
  10. Clinically significant abnormal ECG at screening as evaluated by the Investigator.
  11. Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening.
  12. 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 14 units of alcohol per week (one unit of alcohol equals about 250 mL of beer, 1 glass of wine, or 20 mL of spirits).
  13. Habitual smoking, i.e., daily smoking or more than 7 cigarettes/week within the last 3 months prior to screening. Patients have to accept refraining from smoking while at the clinical site.
  14. Patients 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.
  15. Surgery or trauma with significant blood loss within the last 2 months prior to screening.
  16. Any condition interfering with trial participation or evaluation or that could be hazardous to the patient.
  17. Severe hypoglycaemic events within one year prior to screening, as judged by the Investigator.
  18. Significant changes in basal insulin within 3 weeks before screening, as judged by the Investigator.
  19. Clinically relevant diabetic complications (macrovascular disease with symptoms or signs of coronary artery disease or peripheral vascular disease, microvascular disease with symptoms or signs of neuropathy, gastroparesis, retinopathy, nephropathy, or poor blood glucose control with polyuria, polydipsia, or weight loss), as judged by the Investigator.
  20. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using highly effective contraceptive methods (highly effective contraceptive methods are considered those with a failure rate less than 1% undesired pregnancies per year including surgical sterilisation, hormonal intrauterine devices (coil), oral hormonal contraceptives, sexual abstinence or a surgically sterilised partner) or postmenopausal women being amenorrheic for less than 1 year with serum FSH level <= 40 IU/L and not using highly effective contraceptive methods during the trial and until one month after completion of the trial.
  21. Male who is sexually active and not surgically sterilized who or whose partner(s) is not using highly effective contraceptive methods (highly effective contraceptive measures include surgical sterilisation, hormonal intrauterine devices [coil], oral hormonal contraceptives, each in combination with spermicide-coated condoms), or who is not willing to refrain from sexual intercourse from the first dosing until one month after last dosing in the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02660008


Locations
Germany
Profil Institut für Stoffwechselforschung GmbH
Neuss, Germany, 41460
Sponsors and Collaborators
Zealand Pharma
Investigators
Principal Investigator: Ulrike Hövelmann, MD Profil Institut für Stoffwechselforschung GmbH

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Zealand Pharma
ClinicalTrials.gov Identifier: NCT02660008     History of Changes
Other Study ID Numbers: ZP4207-15126
First Posted: January 21, 2016    Key Record Dates
Last Update Posted: June 15, 2016
Last Verified: June 2016

Additional relevant MeSH terms:
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon
Glucagon-Like Peptide 1
Hypoglycemic Agents
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins