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

NCT04848714 | Completed Phase 1 FDA Drug

• 1 other identifier: AS/BW/ENE-21/0003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Latrodectism

Keywords

Latrodectus envenomation; Black Widow; Equine immune; F(ab´)2

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (7)

• Physical examination

  Baseline, 2, 3, 4, 6, 10, 14 and 21 days

• Sitting blood pressure (mmHg)

  Baseline, 2, 3, 4, 6, 10, 14 and 21 days

• Pulse rate (p/m)

  Baseline, 2, 3, 4, 6, 10, 14 and 21 days

• Respiratory rate (rr)

  Baseline, 2, 3, 4, 6, 10, 14 and 21 days

• Axillary-body temperature (°C)

  Baseline, 2, 3, 4, 6, 10, 14 and 21 days

Study Arms (1)

Group A: ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2]

EXPERIMENTAL

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

Interventions

ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab)2] lyophilized powder for solution 10 mL DRUG

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.

Also known as: ANAWIDOW

Group A: ANAWIDOW [antivenin latrodectus (black widow) equine immune F(ab´)2]

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Laboratorios Silanes S.A. de C.V.: lead
• Rare Disease Therapeutics Inc.: collaborator

Study Sites (1)

Laboratorio Silanes, S.A. de C.V.

Mexico City, Mexico City, 11000, Mexico

Location

Related Publications (4)

• Ryan NM, Buckley NA, Graudins A. Treatments for Latrodectism-A Systematic Review on Their Clinical Effectiveness. Toxins (Basel). 2017 Apr 21;9(4):148. doi: 10.3390/toxins9040148.

  PMID: 28430165 BACKGROUND

• Vazquez H, Chavez-Haro A, Garcia-Ubbelohde W, Mancilla-Nava R, Paniagua-Solis J, Alagon A, Sevcik C. Pharmacokinetics of a F(ab')2 scorpion antivenom in healthy human volunteers. Toxicon. 2005 Dec 1;46(7):797-805. doi: 10.1016/j.toxicon.2005.08.010. Epub 2005 Sep 28.

  PMID: 16197974 BACKGROUND

• Offerman SR, Daubert GP, Clark RF. The treatment of black widow spider envenomation with antivenin latrodectus mactans: a case series. Perm J. 2011 Summer;15(3):76-81. doi: 10.7812/TPP/10-136.

  PMID: 22058673 BACKGROUND

• Dart RC, Bush SP, Heard K, Arnold TC, Sutter M, Campagne D, Holstege CP, Seifert SA, Lo JCY, Quan D, Borron S, Meurer DA, Burnham RI, McNally J, Garcia-Ubbelohde W, Anderson VE. The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(ab')2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial. Ann Emerg Med. 2019 Sep;74(3):439-449. doi: 10.1016/j.annemergmed.2019.02.007. Epub 2019 Mar 27.

  PMID: 30926190 BACKGROUND

Related Links

• USFDA prescribing information ANAVIP® Crotalidae Immune F(ab')2 (Equine) Lyophilized Powder for Solution for Injection for Intravenous Use Only; Initial: 05/06/2015
• Hilda Vázquez, Universidad Nacional Autónoma de México, Pharmacokinetics of a F(ab')(2) scorpion antivenom in healthy human volunteers
• USFDA prescribing information ANASCORP® Centruroides (Scorpion) Immune F(ab')2 (Equine) Injection Lyophilized for Solution for intravenous use only; Revised: July 2011
• Antivenin, black widow spider (Rx), Brand and Other Names: Antivenin (Latrodectus mactans), Medscape, Adverse Effects
• A Phase III Multicenter Clinical Trial of Analatro® \[Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2\] in Patients with Systemic Latrodectism; Instituto Bioclon S.A. de C.V
• USFDA. Retention of Bioavailability and Bioequivalence Testing Samples
• Guideline for Good Clinical Practice, E6 (R2), International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use

MeSH Terms

Conditions

Spider Bites

Interventions

Solutions

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Federico A Arguelles Tello, M.D

  Avant Santé Research Center S.A. de C.V

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 19, 2021
• Study Start: July 1, 2021
• Primary Completion: August 15, 2021
• Study Completion: February 15, 2022
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)