Pharmacokinetic Study Protocol of ANAWIDOW Lyophilized Powder for Solution for Intravenous Use in Fasting Conditions

Study Overview
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Brief Summary
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A single-dose, open-label, single-treatment, single-period pharmacokinetic study under fasting conditions, in 12 healthy adult. To evaluate the single dose pharmacokinetic profile ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2] lyophilized powder for solution 10 mL (dose: 3x10 mL vials) for intravenous use.

Detailed Description
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To evaluate the single dose pharmacokinetic profile ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2] lyophilized powder for solution 10 mL (dose: 3x10 mL vials) for intravenous use of Laboratorios Silanes, S.A. de C.V. in healthy adult human male and female subjects under fasting conditions. To assess the safety of single dose of ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2] lyophilized powder for solution 10 mL (dose: 3x10 mL vials) for intravenous use in healthy adult human male and female subjects under fasting conditions. In a minimum of 12 healthy adult. In this study, all subjects will be required to fast overnight for at least 10.00 hours prior to dosing at least 04.00 hours post-dose. In this study, 3 ANAWIDOW 10 mL vials (3x10 mL) will be administered after diluting with normal saline solution up to 50 mL as intravenous infusion over 30 minutes. The solution will be infused through a 20-gauge catheter placed in the subject's left or right hand antecubital fossa at room temperature under fasting conditions.

Official Title
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Pharmacokinetic Study of ANAWIDOW [Antivenin Latrodectus (Black Widow) Equine Immune F(ab´)2] Solution 10 mL for Intravenous Use of Laboratorios Silanes, S.A. de C.V. in Healthy Adult Male and Female Subjects Under Fasting Conditions.

Conditions
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Latrodectism

Intervention / Treatment
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* Drug: ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab)2] lyophilized powder for solution 10 mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male and female subjects aged between 18 and 55 years (both inclusive). Subject is a light or non- or ex-smoker (A light smoker 1 being defined as someone who is smoking ≤ 9 cigarettes per day and an ex-smoker being defined as someone who completely stopped smoking for at least 6 months before screening): If any subject stops smoking during last 6 months before day of 1 of the study and smoke ≤ 9 cigarettes per day, the subject will also be considered as a light-smoker. With a weight ≥ 50.00 kg. With a body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 24.9 kg/m2. Found healthy according to the clinical laboratory results and physical examination (performed within 21 days prior to the dosing of the study). Have a normal 12-lead ECG and vital signs. Have laboratory test results within the laboratory's stated normal range, if not within this range, they must lack of clinical significance as judged by the PI or responsible physician. If the subject of the study is female and childbearing potential / fertile (a woman is considered fertile after menstruation and until she becomes postmenopausal, unless she is permanently sterile), and agrees to use ONE of the following methods during the study: 21 days before of the dosage and up to at least 28 days after the last administration of the study medication. 9. Women not considered of childbearing / fertile if they meet ONE of the following points: Postmenopausal for at least 1 year Premenopausal woman with ONE of the following: hysterectomy bilateral salpingectomy bilateral oophorectomy The subject must be willing to use ONE of the following methods for 21 days before study drug dosing and at least 28 days after administration of the study medication; Willing to remain abstinent. Willing to use a male condom plus an additional contraceptive method. Be able to communicate effectively and voluntarily agreed to participate in this study by signing written informed consent after being informed sufficiently about study aspects like objectives, study procedures, characteristics of the investigational drug, expected adverse events. Subject willing to adhere to protocol requirements as evidenced by written informed consent approved by REC & RC. Exclusion Criteria: - Have any history of allergy or hypersensitivity to protein products of horse origin or IG or F(ab) or F(ab)2 or to any of its metabolites/derivatives or related drugs or excipients. Or Study drug is contraindicated for medical reasons to the subject as per protocol section 3.7 Have a positive test result for hepatitis B surface antigen (HBs Ag), hepatitis C virus antibody (HCV Ab), HIV antibodies (types 1 and 2) and/or VDRL. Have any history or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, hematological, dermatological, neurological or psychiatric disease or disorder (e.g., subjects with uncontrolled hypertension, phaeochromocytoma, carcinoid, thyrotoxicosis, bipolar depression, schizoaffective disorder and acute confusional states). Presence of gastrointestinal, hepatic or kidney disease, or surgery or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects. Have a history of alcohol abuse or drug abuse. Have a history of smoking ≥ 10 cigarettes per day during the last 6 months prior to screening. History or presence of cancer. Have any history of gastrointestinal ulcers / intestinal bleeding. Have history of difficulty for donating blood. Have clinically significant abnormal laboratory tests results. Have a systolic blood pressure < 90 or > 140 mmHg or diastolic blood pressure is < 60 or > 90 mmHg. Have a pulse rate less than 60 bpm or greater than 100 bpm (lower range will be accepted up to 45 bpm in case of athlete). Have used any prescribed medication during the last 14 days preceding the first dosing, or use OTC, herbal products during the last 7 days or use medicinal enzyme inhibitors / inducers during las 30 days preceding the dosing. Have participated in a drug research study or donated blood within the last 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2]<br>ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2] lyophilized powder for solution 10 mL | Drug: ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab)2] lyophilized powder for solution 10 mL<br>* Antivenin latrodectus (black widow) equine immune F(ab)2] lyophilized powder for solution 10 mL for intravenous use [parenteral formulation]; hence, a single-dose fasting pharmacokinetic study is planned.<br>* Other names: ANAWIDOW;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration following the treatment (Cmax). | To evaluate the single dose pharmacokinetic profile ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2] lyophilized powder for solution 10 mL, employing the maximum observed concentration following the treatment (Cmax). | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 
| The area under the curve from time zero to the last measurable concentration (AUC 0-t)using the linear trapezoidal linear-interpolation method. | To evaluate the single dose pharmacokinetic profile ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2] lyophilized powder for solution 10 mL, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t) using the linear trapezoidal linear-interpolation method. | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 
| The area under the curve from time zero to infinity calculated (AUC 0-inf). | The area under the curve from time zero to infinity calculated (AUC 0-inf). Where AUC0-inf = AUC0-t + Ct/ λz, Ct is the last measurable concentration, and λz is the terminal elimination rate constant. | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 
| Time of the maximum measured concentration (Tmax). | To evaluate the single dose pharmacokinetic profile ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2] lyophilized powder for solution 10 mL, employing the time of the maximum measured concentration (Tmax). | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 
| First order rate constant associated with the terminal portion of the curve (log-lineal), Lambda_z (Kel). | This is estimated via linear regression of time vs log concentration data. This parameter will be calculated using at least three or more non-zero serum concentration values. | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 
| The elimination half-life (HL_Lambda_z (t½)) | The elimination half-life will be calculated as 0.693/ λz. | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 
| Vd (Volume of distribution) | A(t) (mg) / C(t) (mg/L) [A(t) represents the amount of drug in the body at time = t & C(t) represents serum / plasma concentration of the drug at time = t] | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 
| Clearance (CL) | CL (body) = Kel x Vd (volume/hour) | Baseline, 00.08, 00.167, 00.25, 00.34, 00.50, 00.67, 00.83, 01.00, 01.50, 02.00, 04.00, 06.00, 12.00, 24.00,and 2, 3, 4, 6, 10, 14 and 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical examination | Physical examination will be performed before check-in of study period and may also be performed at any time during the study conduct if judged necessary by the physician. | Baseline, 2, 3, 4, 6, 10, 14 and 21 days | 
| Sitting blood pressure (mmHg) | Vital signs will be measured and registered at the time of check-in, prior to dosing, at 01.00, 03.00 and 05.00 hours (within a range of ± 45 minutes) after the same and before the check-out. | Baseline, 2, 3, 4, 6, 10, 14 and 21 days | 
| Pulse rate (p/m) | Vital signs will be measured and registered at the time of check-in, prior to dosing, at 01.00, 03.00 and 05.00 hours (within a range of ± 45 minutes) after the same and before the check-out. | Baseline, 2, 3, 4, 6, 10, 14 and 21 days | 
| Respiratory rate (rr) | Vital signs will be measured and registered at the time of check-in, prior to dosing, at 01.00, 03.00 and 05.00 hours (within a range of ± 45 minutes) after the same and before the check-out. | Baseline, 2, 3, 4, 6, 10, 14 and 21 days | 
| Axillary-body temperature (°C) | Vital signs will be measured and registered at the time of check-in, prior to dosing, at 01.00, 03.00 and 05.00 hours (within a range of ± 45 minutes) after the same and before the check-out. | Baseline, 2, 3, 4, 6, 10, 14 and 21 days | 
| Hematology & biochemistry laboratory tests | Hematology & biochemistry laboratory tests will be performed at the end of the study for all the subjects who administered with the study drug | 21 days | 
| Medical examination | It will be performed before check -in, prior to the dosing and before the check-out. Nevertheless, it may also be performed at any time during the study conduct if judged necessary by the physician. | Baseline, 2, 3, 4, 6, 10, 14 and 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Black Widow, Latrodectus envenomation, Equine immune, F(ab´)2