Clinical trial NCT02081950: A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions
Official title: A Single-Dose Study to Examine the Within Subject Variability of Clexane® (80 mg) s.c. in Healthy Adult Subjects Under Fasting Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clexane is Administered to Healthy Volunteers
Keywords: enoxaparin sodium
Lead sponsor: Chemi S.p.A.
Sponsor class: INDUSTRY
First posted: 2014-03-07
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Primary: To examine the within subject variability of Clexane (80 mg) in healthy male and female volunteers administered subcutaneously (s.c.) as a single dose, in two periods, under fasting conditions.

Secondary: To monitor safety during the Treatment Periods.

Detailed description: This was a pilot, open-label study to evaluate the PK of enoxaparin following s.c. administrations of 80 mg Clexane, on 2 different occasions, in 14 healthy adult subjects.

The study comprised a Screening Visit and 2 Treatment Periods (1 and 2). Screening (Day -14 to Day -1): Screening assessments were carried out within 14 days before administration of the first dose of Clexane. Eligible subjects were asked to return for Treatment Period 1.

Treatment Periods 1 and 2 (Day 0 to Day 26): Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Final confirmation of eligibility was made prior to dosing during Treatment Period 1. Confirmation of ongoing eligibility was made prior to dosing during Treatment Period 2.

Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). During each Treatment Period, subjects resided at the Clinical Unit. Study drug was administered on the morning of Day 1 following an overnight fast. Pharmacokinetic (PK) samples were collected pre-dose and up to 36 h post-dose (x14 samples) for the measurement of enoxaparin. Safety was also evaluated at specified times throughout the study. There were at least 7 days between each dose administration. The Post-Study Follow-Up was conducted on Day 2 of Treatment Period 2 after completion of the 36 h PK blood sampling and vital sign check.

Eligibility criteria: Inclusion Criteria:

* Healthy male or female volunteer between 18 and 55 years of age.
* Female subject of child bearing potential with a negative pregnancy test at the Screening Visit and willing to use 2 effective methods of contraception from Day 1 until 3 months afterwards.
* Subject with no clinically significant abnormal serum biochemistry, haematology, coagulation factors and urine examination values within 14 days of the first dose.

Exclusion Criteria:

* Female subject with weight \< 45 kg or male subject with weight \< 57 kg.
* Subject with clinically relevant abnormal physical findings which could interfere with the objective of the study.
* Subject with clinically relevant abnormal laboratory values indicative of physical illness; Hemoglobin \<13 g/dL; Absolute platelet count below 100 x 109/L.
* 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. In addition, history or presence of: alcoholism or drug abuse within the past year; clotting disorders; gastric or duodenal ulcers; hypertension; retinopathy; deep venous thrombosis; pulmonary embolism; GI bleeding.
* Subject with any clinically significant illness within 4 weeks prior to dosing.
* Subject with recent use of NSAID and/or aspirin (within 4 weeks of first dose) or the use of any pharmacological agents known to significantly induce or inhibit drug-metabolizing enzymes within 30 days of the first dose. No subject may take any antibiotic agent known to interfere with intestinal microflora within 30 days of the first dose. Subjects with any medical condition requiring regular treatment with prescription drugs.
* Subject with recent severe trauma, surgery (eye surgery), and/or lumbar puncture;
* Female subject who was pregnant or lactating.
* Subject who was a vegetarian.
* Subject who, through completion of the study, would have donated in excess of 500 mL of blood and/or plasma within the previous 3 months.
* Subject who regularly consumed excessive amounts of alcohol.
* Subject who consumed excessive amount of caffeine (\> 5 cups of coffee or equivalent per day).
* Subject who was a smoker (cigarettes and tobacco-related products), or ex-smoker who had smoked in the 3 months preceding the study. Subjects were tested for urinary cotinine at screening.
* Subjects who could not tolerate venepuncture.
* Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
* Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months.

Primary outcomes:
measure: Anti-FXa Cmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa AUC0-t
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa AUC0-inf
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIa Cmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIA AUC0-t
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIA AUC0-inf
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
Secondary outcomes:
measure: Anti-FXa Tmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa Lambda Zeta
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa t1/2
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa Cmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa Tmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIa Tmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIa Lambda Zeta
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIa t1/2
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIa Cmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FIIa Tmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Thrombin/FIIa Generation AUC0-t
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Thrombin/FIIa Generation Cmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Thrombin/FIIa Generation Tmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI Cmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI Tmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI Lambda Zeta
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI T1/2
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI AUC0-t
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI AUC0-inf
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI Tmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: TFPI Cmin
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa/Anti-FIIa Cmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa/Anti-FIIa AUC0-t
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa/Anti-FIIa AUC0-inf
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa/Anti-FIIa Tmax
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa/Anti-FIIa Lambda Zeta
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Anti-FXa/Anti-FIIa t1/2
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
measure: Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
timeFrame: Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.
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: