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Diabetes Mellitus Type 1Phase 2NCT02916251

ZP4207(Dasiglucagon) Administered to T1D Patients to Assess the PK and PD Compared to Marketed Glucagon

A Phase 2 study testing ZP4207(dasiglucagon) glucagon analogue and Glucagon (Native glucagon) in people with Diabetes Mellitus Type 1, run by Zealand Pharma at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The trial is a single-centre, randomised, sequential, cross-over trial assessing pharmacokinetic and pharmacodynamic responses after micro-doses of ZP4207 (dasiglucagon*) administered subcutaneously to patients with type 1 diabetes mellitus under euglycaemic and hypoglycaemic conditions and compared to marketed… Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Diabetes Mellitus Type 1
What is being tested?
ZP4207(dasiglucagon) glucagon analogue and Glucagon (Native glucagon)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteGermany
Study dates
1 Dec 2016to 5 Apr 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • To be included in the trial, patients have to fulfil all of the following criteria:
  • Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedures that would not have been performed during normal management of the patient).
  • Male and female patients with T1DM for at least 1 year, as defined by the American Diabetes Association1.
  • Age between 18 and 64 years, both inclusive.
  • HbA1c < 8.5%.
  • C-peptide negative defined as below the lower limit of quantification.
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  • Stable insulin regimen via an insulin infusion pump for at least 1 month prior to screening.
  • Weight between 60 kg and 90 kg, both inclusive.
  • Patients in good health according to age (medical history, physical examination, vital signs, 12-lead ECGs, lab assessments), as judged by the Investigator.-

Who cannot join

  • Patients meeting any of the following criteria during screening evaluations will be excluded from trial participation:
  • Unable to provide informed consent (e.g., impaired cognition or judgement).
  • 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.
  • Receipt of any medicinal product in clinical development within 3 months prior screening.
  • Previous exposure to ZP4207(dasiglucagon) or previously randomized to this trial.
  • Known or suspected allergy to trial product(s) or related products.
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  • History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
  • History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
  • New onset clinically significant illness within 4 weeks prior to screening, as judged by the Investigator.
  • History of liver disease that is expected to interfere with the anti-hypoglycemia action of glucagon (e.g., liver failure or cirrhosis). Other liver disease (i.e., active hepatitis, steatosis, active biliary disease, any tumor of the liver, hemochromatosis, glycogen storage disease) may exclude the patient if it causes significant compromise to liver function or may do so in an unpredictable fashion.
  • Any history or presence of clinically relevant cardiovascular, pulmonary, respiratory, gastrointestinal, renal, metabolic, endocrinological (with the exception of conditions associated with diabetes mellitus), haematological, dermatological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynaecologic (if female), or infectious disease, or signs of acute illness as judged by the Investigator.
  • Clinically significant abnormal haematology, biochemistry or urinalysis screening tests, as judged by the Investigator. In particular, elevated liver enzymes (AST or ALT > 2 times the upper limit of normal, or bilirubin >1.5 the upper limit of normal) or impaired renal function (elevated serum creatinine values above the upper limit of normal).
  • Hypertension with systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg (excluding white-coat hypertension; therefore, if a repeated measurement shows values within the range, the patient can be included in the trial); a heart rate at rest outside the range of 50-90 beats per minute.
  • 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 and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
  • Inadequate venous access as determined by trial nurse or physician at time of screening
  • Any factors that, in the judgment of the Principal Investigator, would interfere with trial endpoints or the safe completion of the trial procedures.
  • Severe hypoglycaemic events within one year prior to screening, as judged by the Investigator.
  • Increased risk of thrombosis, e.g. patients with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator.
  • Significant history of alcoholism or drug abuse as judged by the Investigator or consuming more than 24 g alcohol per day for men, or more than 12 g alcohol per day for women.
  • A positive result in the alcohol and/or urine drug screen at the screening visit.
  • 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.
  • History of cystic fibrosis, pancreatitis, pancreatic tumor, or any other pancreatic disease besides T1DM
  • History of pheochromocytoma.
  • History of adrenal disease or tumor.
  • Positive to the screening test for Hepatitis Bs antigen or Hepatitis C antibodies and/or a positive result to the test for HIV-1/2 antibodies or HIV-1 antigen.
  • The use of any non-prescribed systemic or topical medication, except routine vitamins and occasional use of acetylsalicylic acid and paracetamol within 2 weeks prior to randomization (and if female with the exception of hormonal contraception or menopausal hormone replacement therapy).
  • Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening.
  • 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 the end of the trial (Visit 6).
  • Females of childbearing potential who are pregnant (positive urine human chorionic gonadotropin [HCG]), 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). Females who are postmenopausal can participate in the study without using adequate contraceptive methods. Postmenopausal is defined as women aged < 52 years and being amenorrheic for more than one year with serum FSH level > 40 IU/L or aged >= 52 years and being amenorrheic for less than one year and with serum FSH level > 40 IU/L or aged >= 52 years being amenorrheic for more than one year.
  • -

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Profil Institut für Stoffwechselforschung GmbH

    Neuss, North Rhine-Westphalia, 41460

Other trials in Germany

About this study

Official title: Randomised, Sequential, Cross-over Trial Assessing PK and PD Responses After Micro-doses of ZP4207 Administered s.c. to Patients With T1D Under eu- and Hypoglycemic Conditions and With Reference to Freshly Reconstituted Lyophilized Glucagon

The trial is a single-centre, randomised, sequential, cross-over trial assessing pharmacokinetic and pharmacodynamic responses after micro-doses of ZP4207 (dasiglucagon*) administered subcutaneously to patients with type 1 diabetes mellitus under euglycaemic and hypoglycaemic conditions and compared to marketed glucagon.

*dasiglucagon is the proposed International Nonproprietary Name (pINN) for ZP4207

Read the detailed description

Seventeen (17) adult patients with T1DM treated with continuous subcutaneous insulin infusion (insulin pumps, CSII) will be randomized and take part at four dosing visits. The dosing visits are separated by 3-7 days. For the three lowest dose levels (0.03 mg, 0.08 mg, and 0.2 mg) the patients will receive two doses of ZP4207(dasiglucagon) (the first at euglycaemic and the second at hypoglycaemic conditions) and one dose of glucagon at euglycaemic conditions at visit 2-4. The first two dose administrations (Day 1, visit 2-4) will be separated by at least five hours. The third dose, which is ZP4207(dasiglucagon) during hypoglycemia, will for all dosing visits be administered the next morning after a standardized carbohydrate-rich meal in the evening before. The patients will stay at the clinical site over night between Day 1 and Day 2. The dose of 0.6 mg will only be administered for ZP4207(dasiglucagon). The order of the micro-dose levels as well as the order of the treatment, ZP4207(dasiglucagon) vs. glucagon, will be randomized. For all patients the 0.6 mg dose of ZP4207(dasiglucagon) will be administered at visit 5.

For each dose level there will be 2 sets of PK/PD profiles for ZP4207(dasiglucagon), one initiated during euglycaemia and another during hypoglycaemia. Each patient enrolled will therefore provide a total of 11 PK/PD profiles covering four different dose levels; 8 profiles from ZP4207(dasiglucagon) and 3 profiles from glucagon

Being tested
ZP4207(dasiglucagon) glucagon analogue, Glucagon (Native glucagon)
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZP4207(dasiglucagon) glucagon analogueDrug

    Also called dasiglucagon

    Cross-over design with single s.c. administration in euglycemic and hypoglycemic T1D

  • Glucagon (Native glucagon)Drug

    Also called Lilly Glucagon

    Cross-over design with single s.c. administration in euglycemic T1D

Study groups in NCT02916251
Study groupRoleWhat they receive
ZP4207(dasiglucagon)ExperimentalIntervention: ZP4207(dasiglucagon) glucagon analogue (4 mg/mL) planned doses: 0.03, 0.08, 0.2 and 0.6 mg at euglycemic and hypoglycemic conditions.
Receives: Drug: ZP4207(dasiglucagon) glucagon analogue
Glucagon (Native glucagon)Active comparatorIntervention: Glucagon (Native glucagon) 1 mg/mL as active comparator planned doses: 0.03, 0.08 and 0.2 mg at euglycemic conditions.
Receives: Drug: Glucagon (Native glucagon)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PK endpoint for ZP4207(dasiglucagon) and baseline adjusted glucagon: AUC 0-240 min

    Area under the curve from 0-240 min

    Measured: AUC 0-240 min during all treatment periods (V2-V5)

  2. PK endpoint for ZP4207(dasiglucagon) and baseline adjusted glucagon: Cmax

    max. concentration

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Peak of plasma concentration during all treatment periods (V2-V 5)

  3. PK endpoint for ZP4207(dasiglucagon) and baseline adjusted glucagon: tmax

    Time to peak plasma concentration

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Time to peak plasma concentration during all treatment periods (V2-V5)

  4. PD endpoint: Plasma glucose profiles above baseline: AUE 0-240 min

    Area under the effect curve from 0-240 min

    Measured: Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. AUE 0-240 min during all treatment periods (V2-V5)

  5. PD endpoint: Plasma glucose profiles above baseline: CEmax

    Max concentration effect

    Measured: Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. Peak of plasma glucose concentration during all treatment periods (V2-V5)

  6. PD endpoint: Plasma glucose profiles above baseline: tmax

    Time to peak plasma glucose concentration

    Measured: Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing Time to plasma glucose concentration during all treatment periods (V2-V5)

Secondary outcomes (23)

  1. PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: MRT

    Mean residence time

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Mean residence time for ZP4207(dasiglucagon) and baseline adjusted glucagon during all treatment periods (V2-V5)

  2. PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: Vz/f,

    Volume of distribution

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Volume of distribution of plasma ZP4207(dasiglucagon) or glucagon during all treatment periods (V2-V5)

  3. PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: λz

    Terminal elimination rate constant

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Terminal elimination rate constant of ZP4207(dasiglucagon) and baseline adjusted glucagon during all treatment periods (V2-V5)

  4. PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: t½,

    Terminal plasma elimination half-life

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Terminal plasma elimination half-life of ZP4207(dasiglucagon) or glucagon during all treatment periods (V2-V5)

  5. PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: CL/f

    Total body clearance

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Total body clearance of plasma ZP4207(dasiglucagon) or glucagon during all treatment periods (V2-V5)

  6. PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: AUC 0-30min

    Area under the curve from 0-30 min

    Measured: AUC 0-30 min during all treatment periods (V2-V 5)

  7. PK endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: AUC 0-inf

    Area under the curve from 0-inf

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. AUC 0-inf during all treatment periods (V2-V 5)

  8. Insulin concentrations before and after dosing with ZP4207(dasiglucagon) or glucagon:

    Insulin concentrations

    Measured: Pre-dose, 5, 15, 30, 60, 90, 150 and 240 minutes post dosing. Insulin concentrations during all treatment periods (V2-V 5)

  9. PD endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: AUE 0-30min

    Area under the effect curve from 0-30 min

    Measured: AUE 0-240 min during all treatment periods (V2-V5)

  10. PD endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: CE 30min

    Concentration effect at 30 min

    Measured: Concentration effect at 30 min during all treatment periods (V2-V5)

  11. PD endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: t50%CE, early

    Time to half concentration effect

    Measured: Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. Time to half concentration effect (t50%CE, early) during all treatment periods (V2-V5)

  12. PD endpoints for ZP4207(dasiglucagon) and baseline adjusted glucagon: t10%CE, late

    Time to 90% decrease from CEmax

    Measured: Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. Time to 90% decrease from peak concentration effect during all treatment periods (V2-V5)

  13. PD endpoints: Percentage of patients achieving a plasma glucose increase of ≥20 mg/dL within 30 minutes after treatment

    Measured: During all treatment periods (V2-V5) within 30 min after dosing

  14. PD endpoints: Time to plasma glucose increase of ≥20 mg/dL

    Measured: Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. During all treatment periods (V2-V5) - time plasma glucose increase of ≥20 mg/dL after dosing

  15. PD endpoints: Percentage of patients achieving a plasma glucose concentration ≥70 mg/dL within 30 minutes after treatment (insulin-induced hypoglycemia)

    Measured: During all treatment periods (V2-V5) within 30 min after dosing (insulin-induced hypoglycemia)

  16. PD endpoints: Time to plasma glucose concentration of ≥70 mg/dL (insulin-induced hypoglycemia)

    Measured: Pre-dose, 10, 30, 50, 70, 90, 150, 240 minutes post dosing. During all treatment periods (V2-V5) - time plasma glucose increase of ≥70 mg/dL after dosing (insulin-induced hypoglycemia)

  17. Safety endpoints: Number of participants with adverse events

    Includes events from the first trial related activity after the patient has signed the informed consent until Follow up visit.

    Measured: Through study completion. The total trial duration for a patient will be about 5.5 to 12 weeks.

  18. Safety endpoints: Local tolerability of injection site

    Findings in local tolerability by means of the following assessments:

    spontaneous pain

    • pain on palpation
    • itching
    • redness
    • oedema
    • induration/infiltration
    • other these assessments will be reported on a scale of 0 (none), 1 (mild), 2 (moderate) and 3 (severe)

    Measured: Local tolerability assessed pre-dose (within 30 min) and at 0.5, 2, and 4 hours post-dose (each treatment visit and at Follow up visit).

  19. Safety endpoints: Laboratory safety parameters

    Haematology, biochemistry and urinalysis: Changes or findings from baseline (normal ranges) in clinical safety laboratory parameters during the study duration (from Screening, at treatment visits and at Follow up visit).

    Measured: Through study completion. The total trial duration for a patient will be about 5.5 to 12 weeks.

  20. Safety endpoints: Physical examination

    Physical examination: Changes or findings from baseline (normal ranges) in physical examination during the study duration (at Screening and Follow up visit).

    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

    Measured: Through study completion. The total trial duration for a patient will be about 5.5 to 12 weeks.

  21. Safety endpoints: Vital signs

    Diastolic and systolic blood pressure (mmHg) are measured after at least 5 min rest in a supine position. At the screening visit blood pressure is measured in both arms. The blood pressure from the arm with the higher systolic value is transcribed into the CRF and this arm is used for all subsequent measurements of the patient's blood pressure in this trial.

    Pulse (beats per min) measured after at least 5 min rest in a supine position. Body temperature, tympanic (in Celsius). Respiratory frequency (RF/min). Changes or findings from baseline (normal ranges) in vital signs during the study duration (at Screening, at each treatment visit and at Follow up).

    Measured: Through study completion. The total trial duration for a patient will be about 5.5 to 12 weeks.

  22. Safety endpoints: ECGs

    A standard 12-lead electrocardiogram (ECG) will be performed. ECG parameters (Heart rate, PQ, QRS, QT, QTcB) and any abnormality will be recorded and described in the CRF including the Investigator's assessment of clinical significance ('abnormal, not clinically significant' or 'abnormal, clinically significant'). Clinically significant findings at the screening visit should be recorded as concomitant illness.

    At subsequent visits, any clinically significant deterioration of a pre-existing condition as well as any new clinically significant findings will be recorded as AEs.

    Changes or findings from baseline (normal ranges) (Screening visit and at Follow up) in ECGs during the study duration.

    Measured: Through study completion. The total trial duration for a patient will be about 5.5 to 12 weeks.

  23. Safety endpoints: Antidrug antibodies incidences

    Antidrug antibodies analyses will be performed. Changes or findings from baseline (normal ranges) in Antidrug antibodies incidences during the study duration (before first dosing, at last treatment visit and at Follow up).

    Measured: Through study completion. The total trial duration for a patient will be about 5.5 to 12 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2016 (estimated)
  2. Study start1 Dec 2016
  3. Primary completion5 Apr 2017
  4. Study completion5 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02916251
Sponsor's protocol ID
ZP4207-16098
Status last verified
Apr 2017
First submitted
8 Sep 2016
Last updated
21 Apr 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ZP4207(dasiglucagon) glucagon analogue and Glucagon (Native glucagon) in people with Diabetes Mellitus Type 1, run by Zealand Pharma at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PK endpoint for ZP4207(dasiglucagon) and baseline adjusted glucagon: AUC 0-240 min (time frame: AUC 0-240 min during all treatment periods (V2-V5)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02916251.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2017.

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