This is a Phase 1, exploratory, single dose, randomized, double-blind, two-way cross over,
pilot, glucose clamp study to assess pharmacokinetic and pharmacodynamic effects of Gan &
Lee's insulin glargine injection in comparison to the marketed Lantus (US) in subjects with
type 1 diabetes mellitus (T1DM).
1. Female and Male subjects with T1DM, duration ≥12 months.
2. Adults ≥ 18 to ≤ 65 years of age.
3. Body mass index (BMI) ≥ 18.5 to ≤ 30.0 kg/m2.
4. Weight ≥ 50 kg.
5. Fasting serum C-peptide ≤ 0.4 nmol/L, assessed at a plasma glucose concentration >
6. HbA1c ≤ 9.5%.
7. Current stable treatment with insulin (consistent therapy with multiple daily
injections with basal and bolus insulin or CSII).
8. Current stable dose of insulin (± 20% difference in total daily insulin dose) over
the 2-week period prior to screening; total daily dose ≤ 1.2 IU/kg.
9. Female subjects must be non-pregnant and non-lactating. For postmenopausal females
(no menses >12 months); postmenopausal status will be confirmed through testing of
FSH levels ≥ 40 IU/mL at screening for subjects <55 years of age.
10. Ability to provide written informed consent.
1. A subject who has proliferative retinopathy or maculopathy, severe gastroparesis,
and/or severe neuropathy, in particular autonomic neuropathy, as judged by the
2. History of ≥ 2 episodes of severe hypoglycemia (as defined per ADA criteria) or ≥ 1
episodes of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes
leading to hospitalization within 6 months prior to screening.
3. Subjects is on a carbohydrate restricted diet (i.e., a diet < 100 grams per day of
4. Systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg at
screening. Treatment with no more than 2 antihypertensive medications must be with
stable doses for at least 3 months prior to screening.
5. Current use of any drugs (other than insulin) that are known to interfere with
glucose or insulin metabolism, including but not limited to oral corticosteroids,
monoamino oxidase (MAO) inhibitors, growth hormone and non-selective β-blockers, loop
6. Thyroid hormone use not stable during the past 3 months prior to dosing.
7. Hyperlipidemia treatment not on stable dose for ≥ 3 months prior to dosing. (HMG-CoA
reductase inhibitor (statin), a fibrate (i.e. fenofibrate, gemfibrozil) and ezetimibe
are allowed as treatment).
8. Any use of non-steroid anti-inflammatory drugs (NSAIDs) except for low-dose Aspirin
is not allowed within 7 days prior to dosing and on the dosing day.
9. Participation in an investigational study within 30 days prior to dosing or 5
half-lives within the last dose of investigational product whichever is longer.
10. History of any major surgery within 6 months prior to screening.
11. History of any serious adverse reaction or hypersensitivity to insulin, insulin
analogue, any of the product components, or chemically related products.
12. History of renal disease or abnormal kidney function tests at screening (glomerular
filtration rate (GFR) < 60 mL/min/1.73m2 ).
13. Clinically significant abnormal hematology or biochemistry screening tests.
14. Any history of heart disease, defined as symptomatic heart failure (New York Heart
Association class III or IV), myocardial infarction, coronary artery bypass graft
surgery, or angioplasty, unstable angina requiring medication, transient ischemic
attack, cerebral infarct, or cerebral hemorrhage.
15. History of any clinically significant gastrointestinal, cardiovascular,
hematological, psychiatric, renal, hepatic, pancreatic or neurological abnormality as
judged by the Investigator.
16. Personal or family history of hypercoagulability or thromboembolic disease.
17. History of any active infection, other than mild or viral illness within 30 days
prior to dosing as judged by the Investigator.
18. History of alcohol or illicit/recreational drug abuse as judged by the Investigator
within approximately 1 year. (Use of up to 1000 mL beer, 500 mL wine, or 100 mL
distilled spirits is allowed).
19. Smoking > 10 cigarettes or equivalent use of any tobacco product (e.g.nicotine patch)
within 6 months prior to Screening. Subjects must be able to refrain from smoking at
least 1 week prior to admission and during each in-house period.
20. Known history of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab),
or human immunodeficiency virus type 1 (HIV-1) or 2 (HIV-2) antibody.
21. Existence of any surgical or medical condition that, in the judgment of the
Investigator, might interfere with the absorption, distribution or metabolism of the
drugs or the tolerability/safety measurements.
22. Presence of clinically significant physical, laboratory, or electrocardiogram (ECG)
findings (e.g., QTcF > 470 msec for females, > 450 msec for males, LBBB) at Screening
that, in the opinion of the Investigator, may interfere with any aspect of study
conduct or interpretation of results.
23. Donation or loss of > 500 mL of blood or blood product within 56 days of dosing.