Diabetes Mellitus, Type 1Phase 1NCT04236895
PK/PD Biosimilarity Study of Gan & Lee Insulin Glargine Injection vs.US & EU Lantus® in Type 1 Diabetes Mellitus Patients
A Phase 1 study testing Gan & Lee Insulin Glargine Injection in people with Diabetes Mellitus, Type 1, run by Gan and Lee Pharmaceuticals, USA at 2 sites in Germany.
Trial summary
Primary objectives: To demonstrate biosimilarity with regard to the total and maximum pharmacokinetic exposure during one dosing interval (AUC ins. 0-24h, Cins. max) of Gan \& Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes To demonstrate biosimilarity with regard to the total and… Read more about this study
- Who is it for?
- Ages 18 to 64 years, men only
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Gan & Lee Insulin Glargine Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 2 sitesGermany
- Study dates
- 10 Jul 2018to 28 Nov 2018
- 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 64 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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 subject).
- Male subjects with type 1 diabetes mellitus for at least 12 months prior to screening as diagnosed clinically.
- Age between 18 and 64 years, both inclusive.
- Body Mass Index (BMI) between 18.5 and 29.0 kg/m^2, both inclusive.
- HbA1c <= 9.0%.
- Fasting negative C-peptide (<= 0.30 nmol/L).
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- Total insulin dose of < 1.2 (I)U/kg/day.
- Stable insulin regimen for at least 2 months prior to screening (with respect to safety of the subject and scientific integrity of the trial).
- Considered generally healthy (apart from type 1 diabetes mellitus) upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, as judged by the Investigator
Who cannot join
- Known or suspected hypersensitivity to IMPs or related products
- Previous participation in this trial. Participation is defined as randomized
- Receipt of any medicinal product in clinical development within 30 days or 5 half-lives (whichever is longer) before randomization in this trial
- History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction
- Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator
- Any history or presence of clinically relevant comorbidity (with the exception of conditions associated with diabetes mellitus), or signs of acute illness, as judged by the Investigator
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- Proliferative retinopathy or maculopathy (based on a recent (<1.5 years) ophthalmologic examination) and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator
- Recurrent severe hypoglycemia (more than 1 severe hypoglycemic event during the past 6 months) or hypoglycemic unawareness as judged by the Investigator
- Increased risk of thrombosis, e.g. subjects 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 grams alcohol/day
- Symptomatic hypotension or supine blood pressure at screening (after resting for at least 5 min in supine position) outside the range of 90-140 mmHg for systolic or greater than 90 mmHg for diastolic pressure
- Heart rate at rest outside the range of 50-90 beats per minute
- Clinically significant abnormal standard 12-lead ECG after 5 minutes resting in supine position at screening, as judged by the Investigator
- A positive result in the alcohol and/or urine drug screen at the screening visit
- Not able or willing to refrain from smoking and use of nicotine substitute products one day before and during the inpatient period
- 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
- Any medication (prescription and non-prescription drugs) within 14 days before IMP administration, with the exception of occasional use of Paracetamol or NSAIDs
- Blood donation or blood loss of more than 500 mL within the last 3 months
- Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
- Fertile male with female partner(s) without using a highly effective contraceptive method in combination with spermicide-coated condoms from the first dosing until 1 month after dosing
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Profil Mainz GmbH & Co. KG
Mainz, 55116
Profil Institut für Stoffwechselforschung GmbH
Neuss, 41460
About this study
Official title: A Glucose Clamp Trial Investigating the Biosimilarity of Gan & Lee Insulin Glargine Injection (Insulin Glargine 100 U/mL) With US and EU Lantus® Comparator Products in Patients With Type 1 Diabetes Mellitus
Primary objectives:
To demonstrate biosimilarity with regard to the total and maximum pharmacokinetic exposure during one dosing interval (AUC ins. 0-24h, Cins.
Read more
max) of Gan \& Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes
To demonstrate biosimilarity with regard to the total and maximum pharmacodynamic response during one dosing interval (AUC GIR.0-24h, GIR max) of Gan \& Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes
Secondary objectives:
To compare the pharmacokinetic and pharmacodynamic properties of Gan \& Lee Insulin Glargine and of Lantus® (US RLD / EU RP)
To assess the safety and tolerability of Gan \& Lee Insulin Glargine and of Lantus® (US RLD / EU RP)
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Gan & Lee Insulin Glargine Injection
- Keywords
- Diabetes, Diabetes Type 1, Type 1, Basal, Insulin, Glargine, T1DM, Diabetes Mellitus, Insulin Dependent Diabetes
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gan & Lee Insulin Glargine InjectionDrug
All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.
| Study group | Role | What they receive |
|---|---|---|
| Lantus ® US | Active comparator | Insulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens Receives: Drug: Gan & Lee Insulin Glargine Injection |
| Lantus ® EU | Active comparator | Insulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens Receives: Drug: Gan & Lee Insulin Glargine Injection |
| Gan & Lee Insulin Glargine | Experimental | Insulin glargine 100 U/mL in 3 mL pre-filled pens Receives: Drug: Gan & Lee Insulin Glargine Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK endpoint
AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours
Measured: Up to 24 hours
PK endpoint
Cins.max, maximum observed insulin concentration.
Measured: Up to 30 hrs
PD endpoint
AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours.
Measured: Up to 24 hours
PD endpoint
GIR max, maximum observed glucose infusion rate
Measured: Up to 30 hrs
Secondary outcomes (10)
Secondary PK endpoint
AUC ins.0-12h, AUC ins.12 - 24h, AUC ins.0 -inf., areas under the serum insulin concentration curve in the indicated time intervals
Measured: Up to 24 hrs
Secondary PK endpoint
tmax.ins, time to maximum observed serum insulin concentration
Measured: Up to 30 hrs
Exploratory PK endpoint
t½, terminal serum elimination half-life calculated as t½=ln2/λz and
Measured: Up to 30 hrs
Exploratory PK endpoint
λz, terminal elimination rate constant
Measured: Up to 30 hrs
Secondary PD endpoint
AUC GIR.0 - 12h, AUC GIR.12 - 24h, areas under the glucose infusion rate curve in the indicated time-intervals
Measured: Up to 24 hrs
Secondary PD endpoint
AUC GIR.0 - last, area under the glucose infusion rate curve from 0 hours until the end of clamp
Measured: Up to 30 hrs
Secondary PD endpoint
t max.GIR, time to maximum glucose infusion rate
Measured: Up to 30 hrs
Exploratory PD endpoint
Duration of action, time until blood glucose levels is consistently above 150 mg/dL
Measured: Up to 30 hrs
Exploratory PD endpoint
Time to onset of action, time from trial product administration until blood glucose concentration has decreased at least 5 mg/dL from baseline, where baseline is defined as the mean of blood glucose levels from - 6 to - 2 minutes before trial product administration as measured by ClampArt.
Measured: Up to 30 hrs
Safety endpoints
As measured by treatment-emergent adverse events
Measured: Up to 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2020
- Study start10 Jul 2018
- Primary completion28 Nov 2018
- Study completion28 Nov 2018
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 Diabetes Mellitus, Type 1Studies 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
- Crossover
- Model description
- The trial will be a randomized, double-blind, multicenter, single-dose, 3-way crossover, 3-treatment, euglycemic glucose clamp trial in male subjects with type 1 diabetes mellitus
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gan and Lee Pharmaceuticals, USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jia Lu, PhD, Study director, Gan & Lee Pharmaceuticals, USALeona Plum - Mörschel, MD, PD, Principal investigator, Profil Mainz GmbH & Co KG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04236895
- Sponsor's protocol ID
- GL-GLA-CT1002
- Status last verified
- Jan 2020
- First submitted
- 15 Jan 2020
- Last updated
- 22 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Chen W, Lu J, Plum-Morschel L, Andersen G, Zijlstra E, He A, Xie T, Li L, Hao C, Gan Z, Heise T. Pharmacokinetic and pharmacodynamic bioequivalence of Gan & Lee insulin analogues aspart (rapilin(R)), lispro (prandilin(R)) and glargine (basalin(R)) with EU- und US-sourced reference insulins. Diabetes Obes Metab. 2023 Dec;25(12):3817-3825. doi: 10.1111/dom.15281. Epub 2023 Sep 21.
PubMed 37735841
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Glucose Clamp Trial Investigating the Biosimilarity of Gan & Lee Insulin Glargine Injection (Insulin Glargine 100 U/mL) With US and EU Lantus® Comparator Products in Patients With Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT04236895
- Acronym / sponsor ID
- GL-GLA-CT1002
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes, Diabetes Type 1, Type 1, Basal, Insulin, Glargine, T1DM, Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Gan and Lee Pharmaceuticals, USAIndustry (pharma, biotech, devices)
- Study start
- 10 Jul 2018 (actual)
- Primary completion
- 28 Nov 2018 (actual)
- Study completion
- 28 Nov 2018 (actual)
- First posted
- 22 Jan 2020 (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.
Primary objectives:
To demonstrate biosimilarity with regard to the total and maximum pharmacokinetic exposure during one dosing interval (AUC ins. 0-24h, Cins.
max) of Gan \& Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes
To demonstrate biosimilarity with regard to the total and maximum pharmacodynamic response during one dosing interval (AUC GIR.0-24h, GIR max) of Gan \& Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes
Secondary objectives:
To compare the pharmacokinetic and pharmacodynamic properties of Gan \& Lee Insulin Glargine and of Lantus® (US RLD / EU RP)
To assess the safety and tolerability of Gan \& Lee Insulin Glargine and of Lantus® (US RLD / EU RP)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- The trial will be a randomized, double-blind, multicenter, single-dose, 3-way crossover, 3-treatment, euglycemic glucose clamp trial in male subjects with type 1 diabetes mellitus
| Arm | Type | Receives |
|---|---|---|
| Lantus ® US | Active comparator | Drug: Gan & Lee Insulin Glargine InjectionInsulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens |
| Lantus ® EU | Active comparator | Drug: Gan & Lee Insulin Glargine InjectionInsulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens |
| Gan & Lee Insulin Glargine | Experimental | Drug: Gan & Lee Insulin Glargine InjectionInsulin glargine 100 U/mL in 3 mL pre-filled pens |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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 subject).
- Male subjects with type 1 diabetes mellitus for at least 12 months prior to screening as diagnosed clinically.
- Age between 18 and 64 years, both inclusive.
- Body Mass Index (BMI) between 18.5 and 29.0 kg/m^2, both inclusive.
- HbA1c <= 9.0%.
Key exclusion criteria (20 listed)
- Known or suspected hypersensitivity to IMPs or related products
- Previous participation in this trial. Participation is defined as randomized
- Receipt of any medicinal product in clinical development within 30 days or 5 half-lives (whichever is longer) before randomization in this trial
- History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction
- Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator
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 |
|---|---|---|
| Gan & Lee Insulin Glargine InjectionAll IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen. | Drug | Gan & Lee Insulin Glargine, Lantus ® EU, Lantus ® US |
Primary outcome
PK endpoint
Time frame: Up to 24 hours
AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours
PK endpoint
Time frame: Up to 30 hrs
Cins.max, maximum observed insulin concentration.
PD endpoint
Time frame: Up to 24 hours
AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours.
PD endpoint
Time frame: Up to 30 hrs
GIR max, maximum observed glucose infusion rate
10 secondary outcomes
Secondary PK endpoint
Time frame: Up to 24 hrs
Secondary PK endpoint
Time frame: Up to 30 hrs
Exploratory PK endpoint
Time frame: Up to 30 hrs
Exploratory PK endpoint
Time frame: Up to 30 hrs
Secondary PD endpoint
Time frame: Up to 24 hrs
Secondary PD endpoint
Time frame: Up to 30 hrs
Secondary PD endpoint
Time frame: Up to 30 hrs
Exploratory PD endpoint
Time frame: Up to 30 hrs
Exploratory PD endpoint
Time frame: Up to 30 hrs
Safety endpoints
Time frame: Up to 12 Weeks
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 22 Jan 2020.
- Derived from this study: PubMed 37735841Chen W, Lu J, Plum-Morschel L, Andersen G, Zijlstra E, He A, Xie T, Li L, Hao C, Gan Z, Heise T. Pharmacokinetic and pharmacodynamic bioequivalence of Gan & Lee insulin analogues aspart (rapilin(R)), lispro (prandilin(R)) and glargine (basalin(R)) with EU- und US-sourced reference insulins. Diabetes Obes Metab. 2023 Dec;25(12):3817-3825. doi: 10.1111/dom.15281. Epub 2023 Sep 21.
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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.
Jia Lu, PhD study director
Gan & Lee Pharmaceuticals, USA
Leona Plum - Mörschel, MD, PD principal investigator
Profil Mainz GmbH & Co KG
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gan & Lee Insulin Glargine Injection in people with Diabetes Mellitus, Type 1, run by Gan and Lee Pharmaceuticals, USA at 2 sites 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 20 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 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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?
PK endpoint (time frame: Up to 24 hours). The study lists 4 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 NCT04236895, 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 22 Jan 2020.