HypoglycemiaPhase 1NCT03735225
Evaluation of the Safety, Tolerability and Bioavailability of Dasiglucagon Following Subcutaneous (SC) Compared to IV Administration
A Phase 1 study testing Dasiglucagon in people with Hypoglycemia, run by Zealand Pharma at 1 site in Germany.
Trial summary
The purpose of the trial is to characterize the safety and tolerability of dasiglucagon 4 mg/mL following IV administration at increasing doses in healthy volunteers. One cohort of subjects will receive a SC dose of dasiglucagon to characterize the bioavailability of dasiglucagon following SC administration compared… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoglycemia
- What is being tested?
- Dasiglucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteGermany
- Study dates
- 7 Nov 2018to 24 Jun 2019
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 subject).
- Healthy female or male subjects aged between 18 and 45 years, both inclusive.
- Body weight between 60 and 90 kg, both inclusive.
- Subjects in good health according to age (medical history, physical examination, vital signs, and laboratory assessments), as judged by the investigator.
- Systolic Blood Pressure (SBP) ≥90 mmHg, ≤140 mmHg and Diastolic Blood Pressure (DBP) ≤90 mmHg measured after at least 5 min rest in supine position.
- A pulse rate of ≥50 and ≤90 b/min measured after at least 5 min rest in supine position.
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- 12-lead ECG with QTcF < 450 ms, PR < 220 ms and QRS < 110 ms.
- A female subject must meet one of the following criteria:
- Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout the entire duration of the trial from screening until the last follow-up visit. An acceptable method of contraception includes one of the following:
- Total heterosexual sexual abstinence can be used as a method of contraception if this is the participant's preferred lifestyle and the method is established. Periodic sexual abstinence is not an acceptable method of contraception
- Single method (use only one method):
- intrauterine device (IUD),
- hormone rod inserted under the skin,
- male partner's sterilization
- Double method:
- Hormone contraception A) estrogen and / or progesterone oral contraceptives, B) transdermal patch, C) vaginal ring, D) injection in combination with one of the following: a) vaginal cap with spermicide, b) vaginal sponge (only for women who have never given birth), c) condom, d) female condom
- Participant is of non-childbearing potential, if she is either surgically sterilized (ie, by tubal ligation or removal of ovaries), has undergone complete hysterectomy, or is in a menopausal state (i.e., at least one year without menses).
- A male subject who is sexually active and has a female partner who is of childbearing potential, must use a condom throughout the entire duration of the trial from screening and until the last follow-up visit.
- Condoms MUST be combined with one of the following methods:
- IUD,
- hormone rod inserted under the skin,
- vaginal cap with spermicide,
- vaginal sponge (only for women who have never given birth),
- hormone contraception A) estrogen and / or progesterone oral contraceptives, B) transdermal patch, C) vaginal ring or D) injection
- Total heterosexual sexual abstinence can be used as a method of contraception if this is the participant's preferred lifestyle and the method is established. Periodic sexual abstinence is not an acceptable method of contraception.
Who cannot join
- Previous participation in any trial with dasiglucagon. Participation defined as enrolled into trial.
- Known or suspected hypersensitivity to trial product(s) or related products.
- History of severe hypersensitivity to medicines or foods or history of severe medicinal/food induced anaphylactic reaction.
- Receipt of any investigational product within 3 months prior to screening.
- Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating.
- Any history or presence of cancer, except adequately treated (as judged by investigator) basal or squamous cell skin cancer or cervical carcinoma in situ.
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- A history or presence of any clinically significant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, hematological, dermatological, venereal, neurological or psychiatric diseases, or other major diseases at the discretion of the investigator.
- Known cardiovascular disease, arthrosclerosis, angina pectoris, or a history of myocardial infarction or coronary arterial bypass graft/percutaneous coronary intervention.
- Clinically significant illness (eg, systemic infection) within 4 weeks before screening, as judged by the investigator.
- Any significant pre-existing medical condition as well as pre-planned procedures or surgeries.
- Positive results for Hepatitis B antigens, Hepatitis C antibodies and/or human immunodeficiency virus (HIV) 1 antigen or HIV1/2 antibodies, at screening.
- Any clinically significant abnormal hematology, biochemistry, or urinalysis screening tests, as judged by the investigator.
- Any of the following abnormal laboratory parameters at screening:
- alanine aminotransferase (ALT) > upper limit of normal [ULN] + 10%, aspartate aminotransferase (AST) > ULN + 10%,
- Bilirubin > ULN + 20%
- Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR <90 ml/min/1.73 m2 as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 (14).
- Clinically significant abnormal standard 12-lead ECG after 5 min resting in supine position at screening, as evaluated by the investigator.
- Donation of blood or blood loss of more than 500 mL within 12 weeks prior to screening.
- The use of any non-prescribed systemic medication, except routine vitamins and occasional use of acetylsalicylic acid and paracetamol within 14 days prior to randomization.
- A positive result in the alcohol and/or urine drug screen at the screening visit.
- A history of alcoholism or drug abuse as judged by the investigator
- Smokers (defined as a subject who has been smoking within the last 6 month).
- Subjects with mental incapacity or language barriers that 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Doseescalation Trial to Evaluate the Safety and Tolerability of a Single IV Administration of Dasiglucagon and the Bioavailability of Dasiglucagon Following SC Compared to IV Administration in Healthy Subjects
The purpose of the trial is to characterize the safety and tolerability of dasiglucagon 4 mg/mL following IV administration at increasing doses in healthy volunteers. One cohort of subjects will receive a SC dose of dasiglucagon to characterize the bioavailability of dasiglucagon following SC administration compared to IV administration. Furthermore, the trial aims to assess the potential effect of dasiglucagon on corrected QT interval (QTc) prolongation via a concentrationresponse analysis.
Read the detailed description
Hypoglycemia in patients with diabetes is defined as episodes of an abnormally low plasma glucose concentration. Hypoglycemia is a common, unpredictable, and potentially dangerous side effect of treatment of diabetes mellitus, especially with insulin or sulfonylureas.
Dasiglucagon (ZP4207) is a stable peptide analog of human glucagon, available in a ready-to-use liquid formulation. Dasiglucagon is in development for the treatment of severe hypoglycemia in patients with diabetes mellitus. Dasiglucagon is a specific and full glucagon receptor agonist designed to mimic the effects of glucagon, having a fast absorption and elimination (minutes).
- Conditions
- Hypoglycemia
- Being tested
- Dasiglucagon, Placebo
- Medical subject headings
- Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasiglucagonDrug
Also called ZP4207
Dasiglucagon injection
PlaceboDrug
Also called Placebo for Dasiglucagon
Placebo for Dasiglucagon injection
| Study group | Role | What they receive |
|---|---|---|
| IV Dasiglucagon | Experimental | Dasiglucagon 0.1, 0.3, 0.6, 1.5 or 2.0 mg administered IV as a single dose Receives: Drug: Dasiglucagon |
| SC 0.6 mg Dasiglucagon | Experimental | Dasiglucagon 0.6 mg administered SC as a single dose Receives: Drug: Dasiglucagon |
| IV Placebo | Placebo comparator | Placebo 0.1, 0.3, 0.6, 1.5 or 2.0 mg administered IV as a single dose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Change measures from baseline considering nausea, vomiting and diarrhea
Measured: day 1, day 2, day 28
Secondary outcomes (9)
Clinical assessment of local tolerability at injection site by physical examination
Change measures from baseline in pain, redness, itching, edema, induration/infiltration of skin
Measured: day-1, day 1, day 2, day 28
Occurrence of anti-drug antibodies (ADA)
Change measures from baseline
Measured: day 1 and day 28
Plasma dasiglucagon profiles following IV administration, Area Under the Curve (AUC)
Change measures from baseline
Measured: Pre-dose, 5, 15, 25, 40, 60, 80, 100, 120, 140, 180 and 240 min.
Plasma dasiglucagon profiles following SC administration, Area Under the Curve (AUC)
Change measures from baseline
Measured: Pre-dose, 5, 15, 25, 35, 45, 60, 90, 130, 210 and 300 min.
Change-from-baseline in ECG for QTcF
Change measures from baseline
Measured: From day -1 to day 2 and day 28
Change-from-baseline in ECG for heart rate (HR)
Change measures from baseline
Measured: From day -1 to day 2 and day 28
Change-from-baseline in ECG for pulse rate (PR)
Change measures from baseline
Measured: From day -1 to day 2 and day 28
Change-from-baseline in ECG for QRS
Change measures from baseline
Measured: From day -1 to day 2 and day 28
Frequency of treatment-emergent T-wave morphology changes and U-waves by Holter monitoring
Change measures from baseline
Measured: From day -1 to day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2018
- Study start7 Nov 2018
- Primary completion24 Jun 2019
- Study completion24 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypoglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Dose escalation
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christina M Sylvest, MSc Pharm, Study director, Zealand Pharma A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03735225
- Sponsor's protocol ID
- ZP4207-17144
- Status last verified
- Mar 2021
- First submitted
- 10 Oct 2018
- Last updated
- 23 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tehranchi R, Pettersson J, Melgaard AE, Seitz F, Valeur A, Maarbjerg SJ. Dasiglucagon Effects on QTc in Healthy Volunteers: A Randomized, Placebo-Controlled, Dose-Escalation, Double-Blind Study. Curr Ther Res Clin Exp. 2022 Mar 29;96:100668. doi: 10.1016/j.curtheres.2022.100668. eCollection 2022.
PubMed 35464292
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Doseescalation Trial to Evaluate the Safety and Tolerability of a Single IV Administration of Dasiglucagon and the Bioavailability of Dasiglucagon Following SC Compared to IV Administration in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03735225
- Acronym / sponsor ID
- ZP4207-17144
- Conditions
- Hypoglycemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Zealand PharmaIndustry (pharma, biotech, devices)
- Study start
- 7 Nov 2018 (actual)
- Primary completion
- 24 Jun 2019 (actual)
- Study completion
- 24 Jun 2019 (actual)
- First posted
- 8 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the trial is to characterize the safety and tolerability of dasiglucagon 4 mg/mL following IV administration at increasing doses in healthy volunteers. One cohort of subjects will receive a SC dose of dasiglucagon to characterize the bioavailability of dasiglucagon following SC administration compared to IV administration. Furthermore, the trial aims to assess the potential effect of dasiglucagon on corrected QT interval (QTc) prolongation via a concentrationresponse analysis.
Detailed description
Hypoglycemia in patients with diabetes is defined as episodes of an abnormally low plasma glucose concentration. Hypoglycemia is a common, unpredictable, and potentially dangerous side effect of treatment of diabetes mellitus, especially with insulin or sulfonylureas.
Dasiglucagon (ZP4207) is a stable peptide analog of human glucagon, available in a ready-to-use liquid formulation. Dasiglucagon is in development for the treatment of severe hypoglycemia in patients with diabetes mellitus. Dasiglucagon is a specific and full glucagon receptor agonist designed to mimic the effects of glucagon, having a fast absorption and elimination (minutes).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Dose escalation
| Arm | Type | Receives |
|---|---|---|
| IV Dasiglucagon | Experimental | Drug: DasiglucagonDasiglucagon 0.1, 0.3, 0.6, 1.5 or 2.0 mg administered IV as a single dose |
| SC 0.6 mg Dasiglucagon | Experimental | Drug: DasiglucagonDasiglucagon 0.6 mg administered SC as a single dose |
| IV Placebo | Placebo comparator | Drug: PlaceboPlacebo 0.1, 0.3, 0.6, 1.5 or 2.0 mg administered IV as a single dose |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (25 listed)
- 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 subject).
- Healthy female or male subjects aged between 18 and 45 years, both inclusive.
- Body weight between 60 and 90 kg, both inclusive.
- Subjects in good health according to age (medical history, physical examination, vital signs, and laboratory assessments), as judged by the investigator.
- Systolic Blood Pressure (SBP) ≥90 mmHg, ≤140 mmHg and Diastolic Blood Pressure (DBP) ≤90 mmHg measured after at least 5 min rest in supine position.
Key exclusion criteria (23 listed)
- Previous participation in any trial with dasiglucagon. Participation defined as enrolled into trial.
- Known or suspected hypersensitivity to trial product(s) or related products.
- History of severe hypersensitivity to medicines or foods or history of severe medicinal/food induced anaphylactic reaction.
- Receipt of any investigational product within 3 months prior to screening.
- Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasiglucagonAlso: ZP4207Dasiglucagon injection | Drug | IV Dasiglucagon, SC 0.6 mg Dasiglucagon |
| PlaceboAlso: Placebo for DasiglucagonPlacebo for Dasiglucagon injection | Drug | IV Placebo |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: day 1, day 2, day 28
Change measures from baseline considering nausea, vomiting and diarrhea
9 secondary outcomes
Clinical assessment of local tolerability at injection site by physical examination
Time frame: day-1, day 1, day 2, day 28
Occurrence of anti-drug antibodies (ADA)
Time frame: day 1 and day 28
Plasma dasiglucagon profiles following IV administration, Area Under the Curve (AUC)
Time frame: Pre-dose, 5, 15, 25, 40, 60, 80, 100, 120, 140, 180 and 240 min.
Plasma dasiglucagon profiles following SC administration, Area Under the Curve (AUC)
Time frame: Pre-dose, 5, 15, 25, 35, 45, 60, 90, 130, 210 and 300 min.
Change-from-baseline in ECG for QTcF
Time frame: From day -1 to day 2 and day 28
Change-from-baseline in ECG for heart rate (HR)
Time frame: From day -1 to day 2 and day 28
Change-from-baseline in ECG for pulse rate (PR)
Time frame: From day -1 to day 2 and day 28
Change-from-baseline in ECG for QRS
Time frame: From day -1 to day 2 and day 28
Frequency of treatment-emergent T-wave morphology changes and U-waves by Holter monitoring
Time frame: From day -1 to day 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Derived from this study: PubMed 35464292Tehranchi R, Pettersson J, Melgaard AE, Seitz F, Valeur A, Maarbjerg SJ. Dasiglucagon Effects on QTc in Healthy Volunteers: A Randomized, Placebo-Controlled, Dose-Escalation, Double-Blind Study. Curr Ther Res Clin Exp. 2022 Mar 29;96:100668. doi: 10.1016/j.curtheres.2022.100668. eCollection 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christina M Sylvest, MSc Pharm study director
Zealand Pharma A/S
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dasiglucagon in people with Hypoglycemia, 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 25 inclusion and 23 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 23 Mar 2021. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: day 1, day 2, day 28). 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 NCT03735225, which also lists 1 linked publication.
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 23 Mar 2021.