Clinical trial NCT02232802: Bioavailability Study of Enoxaparin Sodium Chemi and Clexane s.c.
Official title: Comparative, Randomized, Single-dose, 2-way Cross Over Bioavailability Study of Enoxaparin Sodium Chemi (80 mg/0.8mL) and Clexane® (80 mg/0.8mL) s.c. in Healthy Adult Subjects Under Fasting Conditions.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Enoxaparin Sodium is Administered to Healthy Volunteers
Lead sponsor: Chemi S.p.A.
Sponsor class: INDUSTRY
First posted: 2014-09-05
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: * The primary objective of the trial is to assess the single-dose relative bioavailability of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by subcutaneous (s.c.) injection, under fasting conditions in healthy volunteers.
* The secondary objective of the trial is to assess safety and tolerability of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by s.c. injection, under fasting conditions in healthy volunteers.

Detailed description: This is an open-label, randomised, single-dose, 2-way crossover study to determine the comparative bioavailability of enoxaparin sodium from the Chemi Enoxaparin s.c. (80 mg/0.8mL) with that from the reference IMP, Clexane® s.c. (80 mg/0.8mL), following single dose administration in healthy male and female subjects.

Each subject received each treatment over two separate treatment periods under fasting conditions. Each dosing day for male subjects will be separated by a washout period of at least 7 days. The study comprised a pre-study screen (within 14 days of the first dose), followed by 2 Treatment Periods (1 and 2). During each treatment period, subjects will reside at Simbec from the evening before dosing (Day 1), until at least 36 h post dose (evening of Day 2). On admission (Day -1), subjects will provide a urine sample for a drugs of abuse screen; this sample will also be tested to confirm a negative pregnancy result in female volunteers.

A single dose of the randomised treatment will be given on the morning of Day 1 following an overnight fast and blood PK/PD samples collected from pre-dose up to 36 h post dose (14 samples). Safety will also be evaluated at specified times throughout the study.

The post study visit will be conducted on Day 2 (36 h post-dose) of Treatment Period 2.

Eligibility criteria: Inclusion Criteria:

* Healthy male or female volunteer between 18 and 55 years of age.
* Subject with a BMI of 18-30 (Body Mass Index = Body weight (kg) / \[Height (m)\]2)
* Subject with no clinically significant abnormal serum biochemistry, haematology, coagulation factors and urine examination values within 14 days of the first dose.
* Subject with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) and vital signs determined within 14 days of the first dose.
* Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (HbsAg) and hepatitis C virus antibody (HCV) results.

Exclusion Criteria:

* Subject with hypersensitivity or idiosyncratic reaction to enoxaparin and/or low molecular weight heparins, and/or pork products.
* Subject with a relevant history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease. Or with history or presence of alcoholism or drug abuse;
* Subject with clinically relevant abnormal physical findings or clinically relevant abnormal laboratory values indicative of physical illness;
* Female subject who is pregnant or lactating
* Female subject with weight \< 45 kg or male subject with weight \< 57 kg.

Primary outcomes:
measure: Cmax (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC0-t (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Secondary outcomes:
measure: AUC0-inf (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Tmax (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Lambda Zeta (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: t1/2 (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Tmin (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC%ex (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Cmin (Anti-FXa and Anti-FIIa)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Cmax (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Cmax (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC0-t (Derived Thrombin Generation)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Cmin (Derived Thrombin Generation)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Tmin (Derived Thrombin Generation)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Tmax (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Cmin (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Tmin (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: T1/2 (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC0-t (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC0-inf (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: T1/2 (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Cmin (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Tmin (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: AUC%ex (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Tmax (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
measure: Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)
timeFrame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Other outcomes:
Locations:
city: Merthyr Tydfil
country: United Kingdom
facility: Simbec Research Ltd
Study officials:
affiliation: Italfarmaco S.p.A.
name: Paolo Bettica, MD
role: STUDY_DIRECTOR
References: