A Study to Evaluate the Intramuscular Administration of Scopolamine

NCT04314713 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: S-16-14
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

To characterize the safety and tolerability profile of ascending doses of scopolamine hydrobromide trihydrate (Scopolamine HBT) administered by intramuscular (IM) injection. And characterize the pharmacokinetics (PK) of ascending doses of Scopolamine HBT administered by IM injection

Conditions

Medical Countermeasures; Organophosphate Poisoning

Keywords

Scopolamine

Outcome Measures

Primary Outcomes (11)

• Determine Degree and Number of Adverse Events Experienced by Subjects.

  Safety and tolerability profile of ascending doses of scopolamine hydrobromide trihydrate (Scopolamine HBT) administered by intramuscular (IM) injection

  30 Days (+7)

• Cmax of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  Cmax of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• Tmax of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  Tmax of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• Apparent Volume of Distribution (mL/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  Apparent Volume of Distribution (mL/kg) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• t1/2 (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  t1/2 (hr) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• Apparent Clearance (mL/hr/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  Apparent Clearance (mL/hr/kg) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• MRT (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  MRT (hr) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• AUClast (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  AUClast (hr\*ug/mL) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• AUCinfinity (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  AUCinfinity (hr\*ug/mL) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• Cmax/Dose (ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  Cmax/Dose (ug/mL)/(mg/kg) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

• AUCinfinity/Dose (hr*ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection.

  AUCinfinity/Dose (hr\*ug/mL)/(mg/kg) of ascending doses of Scopolamine HBT administered by IM injection.

  30 Days (+7)

Study Arms (6)

Scopolamine HBT 0.005 mg/kg

PLACEBO COMPARATOR

Dose of Scopolamine 0.005mg/kg verses Placebo

Drug: Scopolamine Hydrobromide Trihydrate

Scopolamine HBT 0.007 mg/kg

PLACEBO COMPARATOR

Dose of Scopolamine 0.007mg/kg verses Placebo

Drug: Scopolamine Hydrobromide Trihydrate

Scopolamine HBT 0.011 mg/kg

PLACEBO COMPARATOR

Dose of Scopolamine 0.011mg/kg verses Placebo

Drug: Scopolamine Hydrobromide Trihydrate

Scopolamine HBT 0.014 mg/kg

PLACEBO COMPARATOR

Dose of Scopolamine 0.014mg/kg verses Placebo

Drug: Scopolamine Hydrobromide Trihydrate

Scopolamine HBT 0.021 mg/kg

PLACEBO COMPARATOR

Dose of Scopolamine 0.021mg/kg verses Placebo

Drug: Scopolamine Hydrobromide Trihydrate

Placebo

NO INTERVENTION

Placebo controlled

Interventions

Scopolamine Hydrobromide Trihydrate DRUG

Scopolamine Hydrobromide Trihydrate Intramuscular Injection

Scopolamine HBT 0.005 mg/kg; Scopolamine HBT 0.007 mg/kg; Scopolamine HBT 0.011 mg/kg; Scopolamine HBT 0.014 mg/kg; Scopolamine HBT 0.021 mg/kg

Eligibility Criteria

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

You may qualify if:

• Male or female, 18 to 55 years of age, inclusive, at the time of drug administration
• Without clinically significant abnormities on physical examination at screening or prior to drug administration
• Generally healthy, as determined by medical history review, physical examination, and laboratory testing at screening and prior to drug administration
• Must have a BMI (body mass index) of ≥ 19.0 and ≤ 30.0, and weight range of 55.0 to 85.0 kg at screening or prior to drug administration
• Must have adequate venous access and sufficient upper leg muscle tissue for drug administration
• If female, the subject must be nonpregnant and nonbreastfeeding, and have a negative serum pregnancy test at screening and prior to drug administration
• If female of childbearing potential, the subject must have been using adequate contraception (as defined in Section 5.3.1.5) for at least 3 months prior to drug administration and must agree to use an adequate method of contraception for at least 30 days following drug administration
• Females of nonchildbearing potential are also eligible, defined as a subject who is postmenopausal (continuous amenorrhea for 24 months) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy)
• A male with a female partner of childbearing potential must agree to use a barrier method of contraception (defined as condoms with spermicide) for at least 30 days following drug administration
• If male, must not have past diagnoses of benign prostatic hypertrophy or urinary tract obstruction and must not have on screening history/review of systems symptoms suggestive of urinary tract obstruction (eg, urinary hesitancy, urgency, frequency, or nocturia)
• Nonsmoker/tobacco/nicotine product (including e-cigarettes) user within 3 months of first dosing and must have a total lifetime exposure to cigarettes of \< 15 pack-years
• No evidence of significant neuropsychiatric disorders based on the Brief Psychiatric Rating Scale (BPRS) at screening and prior to drug administration, which is defined as having a global score of ≤ 25 with no score higher than 2 on any one item, with the exception of a score of 1 (ie, Not Present) to disorientation, hallucinatory behavior, and suspiciousness (ie, paranoia)
• No evidence of suicidal ideation or behavior at screening and prior to drug administration, which is defined as having a global score of 0 on the Columbia-Suicide Severity Rating Scale (C-SSRS)
• Ability to read, speak, and comprehend English and a willingness to sign informed consent

You may not qualify if:

• Received any other investigational drug within 30 days prior to drug administration
• Known allergies to any component of the study drug, other belladonna alkaloids, or the recovery medications (physostigmine, atropine, or benzodiazepines \[diazepam or lorazepam\])
• History of migraine headaches or seizures
• History of psychosis or psychotic episodes
• Clinically relevant abnormal physical findings (including vital signs) as determined by the investigator at screening or prior to drug administration that could interfere with the objectives of the study or the safety of the subject
• Has ongoing drug abuse/dependence (including alcohol), recent history (over the past 5 years) of treatment for alcohol or drug abuse, or a current positive alcohol breathalyzer test or current positive urine test for drugs of abuse (as defined in Section 11.1.9.5) at screening or prior to drug administration
• Has consumed Seville orange (bitter orange), grapefruit, grapefruit juice, other grapefruit-containing products, or starfruit within 7 days prior to dosing
• Has consumed caffeine or other xanthine-containing products within 7 days prior to dosing
• Has any specified laboratory values (eg, hematology, serum chemistry, and urinalysis) outside of the normal range for age and sex and deemed clinically significant by the investigator within 30 days before drug administration
• Has positive (reactive) test results for hepatitis B surface antigen, hepatitis C, syphilis, HIV-1, or HIV-2
• Has narrow-angle glaucoma or high intraocular pressures in either or both eyes
• Has pyloric obstruction or urinary bladder neck obstruction
• Has impaired liver or kidney functions
• Clinically relevant electrocardiogram (ECG) abnormalities on any 12-lead ECG obtained at screening or prior to dosing
• ECG with a PR interval ≥ 200 msec at screening or prior to dosing

Sponsors & Collaborators

• Battelle Memorial Institute: lead

Study Sites (1)

Pharmaron

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Organophosphate Poisoning

Condition Hierarchy (Ancestors)

Poisoning; Chemically-Induced Disorders

Results Point of Contact

• Title: Paolo DePetrillo
• Organization: Pharmaron

paolo.depetrillo@pharmaron.com

240-673-0500

Study Officials

• Paolo DePetrillo, MD

  Pharmaron

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blinded, randomized, placebo-controlled
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 19, 2020
• Study Start: June 2, 2020
• Primary Completion: April 6, 2021
• Study Completion: May 6, 2021
• Last Updated: February 19, 2025
• Results First Posted: February 19, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)