Pharmacokinetic (PK) and Safety Study of Plasma-derived Human Butyrylcholinesterase Administered Intravenously

NCT00333515 | Completed Phase 1 DMC

• 1 other identifier: HuBChE-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this placebo-controlled study is to evaluate the safety, tolerability and pharmacokinetics of a single dose regimen of human butyrylcholinesterase (HuBChE) in healthy adults at 3 ascending dosage levels administered IV. HuBChE, which occurs naturally in human plasma, is being evaluated for prophylaxis and treatment in the event of exposure to chemical nerve agents (as employed during chemical warfare or as an act of terrorism). Volunteers in each dosage cohort will be randomized to treatment with HuBChE active drug or normal saline placebo in a 3:1 ratio. The volunteers will remain in the study for 90 (+/- 7) days. For the first 3 days following dose administration, they will remain at the clinical trial site as inpatients and will be closely monitored for patient safety. Afterwards, they will return to the trial site (at pre-determined intervals) as outpatients for 8 further visits, where patient safety will be assessed.

Conditions

Healthy Volunteers; Chemical Terrorism; Chemical Warfare

Keywords

Chemical nerve agent intoxication

Outcome Measures

Primary Outcomes (1)

• Frequence and severity of local and systemic AEs

  until post-infusion Day 90 (+/- 7 days)

Study Arms (2)

1

EXPERIMENTAL

Administration of one of 3 doses (dose escalation) of the active drug (HuBChE). (Dose-escalation proceeds only after safety evaluation and after the previous dosage has been found to be acceptable by an independent Data Safety Monitoring Board.)

Drug: Human Butyrylcholinesterase (HuBChE) derived from human plasma

2

PLACEBO COMPARATOR

Administration of placebo

Drug: Placebo: Normal saline

Interventions

Human Butyrylcholinesterase (HuBChE) derived from human plasma DRUG

Administration via IV infusion at a rate of 50 mg/min (2 mL/min)

1

Placebo: Normal saline DRUG

Administration via IV infusion at a rate of 50 mg/min (2 mL/min)

2

Eligibility Criteria

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

You may qualify if:

• The volunteer is between 18 and 55 years of age (inclusive) at the time of administration of HuBChE.
• The volunteer is in good health as determined by the Investigator (Study Doctor) from a medical history and physical examination.
• The volunteer has clinical chemistry, hematology, coagulation, and urinalysis laboratory values within acceptable ranges or deemed clinically insignificant by the Principal Investigator (PI) and Project Medical Monitor.
• The volunteer has a normal electrocardiogram (ECG) or one with clinically insignificant findings as deemed by the PI.
• The volunteer is willing to have his or her blood samples stored for future HuBChE research studies.
• The volunteer has signed the Informed Consent form (ICF) and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form.
• The volunteer agrees not to donate blood during the trial or for at least 2 months following the 90 day study visit.
• The volunteer is willing to comply with the requirements of the protocol through the post-infusion Day 90 (± 7 days) visit.
• Female volunteers must be of non-childbearing potential (i.e., surgically sterilized or postmenopausal), or must not be pregnant (as indicated by a negative urine pregnancy test within 1 day prior to HuBChE administration) or nursing, and must use two types of acceptable forms of Food and Drug Administration (FDA)-approved birth control methods, including:
• Progesterone only hormonal types of birth control (such as implants or birth control pills) or an intrauterine device (IUD) and
• an additional barrier type of birth control measure (i.e., condoms, diaphragms, cervical caps, etc.) during the period beginning from 30 days before HuBChE administration through completion of the study. Completion of the study is defined as completing the acute phase of the study (Day 45 \[± 3 days\] visit).

You may not qualify if:

• The volunteer demonstrates predisposition to thrombus formation as determined by past medical history, and family history.
• The volunteer has a history of anaphylactoid reaction or other serious adverse reactions to blood products.
• The volunteer has a history of allergic reaction to procainamide or to its metabolite, p-aminobenzoic acid.
• The volunteer has been diagnosed with alcohol or drug abuse within the 12 months prior to study screening or offers a history of alcohol or drug abuse within the 12 months prior to screening.
• The volunteer has a positive result on a urine drug screen that tests for common substances of abuse, such as amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and cannabinoids. (If positive on screen, confirmatory testing shall be performed where applicable.)
• The volunteer has a previous diagnosis of any serious psychiatric disorder. For this purpose, serious psychiatric disorder is defined as illness requiring hospitalization within the previous 12 months; routine administration of more than one medication to control anxiety, mood or sleep disorder; or history of suicide attempt.
• The volunteer has received any blood products or immune globulin in the previous six months.
• The volunteer has donated blood within 56 days prior to receipt of study product (Day 0).
• The volunteer has a deficiency of immunoglobulin A (IgA) as determined on screening.
• The volunteer has a current or past medical history for any condition which, in the opinion of the PI and/or Project Medical Monitor (PMM), might place him or her at risk by participating in the study.
• Personal or family history (in first degree relatives) of significant neuromuscular disease (as determined by the PI).
• Female volunteer is pregnant (must have a negative urine pregnancy test within 1 day of receipt of HuBChE), lactating, or unwilling to use 2 types of an acceptable FDA-approved form of contraception from time of screening through completion of the Day 45 (± 1 day) study visit.
• Current use, receipt within the previous 14 days, or intent to use during the 14 days after receiving drug product of drugs that may be metabolized, inhibited, or otherwise affected by BChE.
• The volunteer has a clinically significant abnormality on the ECG.
• The volunteer has any laboratory values outside acceptable ranges that are clinically significant as assessed by the Investigator and/or PMM. The volunteer tests positive for HIV, HCV, or HBV at screening.

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• DynPort Vaccine Company LLC, A GDIT Company: collaborator

Study Sites (1)

Quintiles Phase 1 Services

Lenexa, Kansas, 66219, United States

Location

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2006
• First Posted: June 5, 2006
• Study Start: January 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: August 1, 2008
• Last Updated: May 5, 2021

Record last verified: 2021-05

Locations

US (1)