A Study to Evaluate the Intramuscular Administration of Scopolamine

Study Overview
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Brief Summary
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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

Detailed Description
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This is a double-blinded, randomized, placebo-controlled, in-clinic, Phase 1, single-dose, IM, sequential dose-escalation study in healthy adults aged 18-55. Healthy volunteers will be assigned to 1 of 5 cohorts of Scopolamine HBT dosage groups: 0.005, 0.007, 0.011, 0.014, or 0.021 mg/kg, or will receive the placebo administered by IM injection to the anterior thigh. In each cohort, 6 to 9 subjects will receive active drug and 2 to 3 subjects will receive placebo. Each cohort will have at least 3 male and 3 female subjects enrolled among the first 8 subjects in the dosing group to ensure that at least 1 male subject and 1 female subject in each dosing group receive active drug. If nonextreme dose-limiting toxicities are observed in any of the cohorts, 4 additional subjects, 3 active and 1 placebo, may be added to each cohort.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Study To Evaluated The Safety, Tolerability, and Pharmacokinetics Of Intramuscular Administration Of Scopolamine Hydrobromide Trihydrate, Injection

Conditions
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Scopolamine Causing Adverse Effects in Therapeutic Use

Intervention / Treatment
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* Drug: Scopolamine Hydrobromide Trihydrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 ECG with QRS duration > 120 msec at screening or prior to dosing ECG RR interval > 1500 msec at screening or prior to dosing ECG with a QTc interval > 450 msec for males or 470 msec for females (QT interval corrected with Fridericia correction [QTcF]) at screening or prior to dosing Systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg at screening or prior to dosing Systolic blood pressure < 90 mm Hg and/or diastolic blood pressure < 50 mm Hg at screening or prior to dosing Currently taking or has taken other antimuscarinic drugs such as phenothiazines, tricyclic antidepressants, antihistamines (including meclizine), meperidine, or other anticholinergics that have weak antimuscarinic activity or that cause drowsiness, including antidepressants, benzodiazepines, alcohol, sedatives (used to treat insomnia), pain relievers, anxiety medicines, and muscle relaxants within 72 hours prior to dosing Has taken, within 14 days of planned dosing, any prescription or nonprescription medication (including home remedies, herbal supplements, or nutritional supplements) unless the PI/subinvestigator, in consultation with the medical monitor, provides a statement justifying that the medication taken will not impact the results of this study (with rare exceptions taking prescriptions drugs will be grounds for exclusion) History of major DSM-5 Axis I or II disorder, or evidence of such disorder at Day -1 as determined via the Structured Clinical Interview for DSM-5, customized Clinical Trials version (SCID-5-CT)

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Scopolamine HBT 0.005 mg/kg<br>Dose of Scopolamine 0.005mg/kg verses Placebo | Drug: Scopolamine Hydrobromide Trihydrate<br>* Scopolamine Hydrobromide Trihydrate Intramuscular Injection<br>|
| Placebo Comparator: Scopolamine HBT 0.007 mg/kg<br>Dose of Scopolamine 0.007mg/kg verses Placebo | Drug: Scopolamine Hydrobromide Trihydrate<br>* Scopolamine Hydrobromide Trihydrate Intramuscular Injection<br>|
| Placebo Comparator: Scopolamine HBT 0.011 mg/kg<br>Dose of Scopolamine 0.011mg/kg verses Placebo | Drug: Scopolamine Hydrobromide Trihydrate<br>* Scopolamine Hydrobromide Trihydrate Intramuscular Injection<br>|
| Placebo Comparator: Scopolamine HBT 0.014 mg/kg<br>Dose of Scopolamine 0.014mg/kg verses Placebo | Drug: Scopolamine Hydrobromide Trihydrate<br>* Scopolamine Hydrobromide Trihydrate Intramuscular Injection<br>|
| Placebo Comparator: Scopolamine HBT 0.021 mg/kg<br>Dose of Scopolamine 0.021mg/kg verses Placebo | Drug: Scopolamine Hydrobromide Trihydrate<br>* Scopolamine Hydrobromide Trihydrate Intramuscular Injection<br>|
| No Intervention: Placebo<br>Placebo controlled | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine degree and number of adverse events experienced by subjects. | To characterize the safety and tolerability profile of ascending doses of scopolamine hydrobromide trihydrate (Scopolamine HBT) administered by intramuscular (IM) injection | 30 Days (+7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine what the what the body does with the movement of drug within the body of Scopolamine HBT after IM Administration. | A goal of this clinical study is to measure Scopolamine HBT immunity remaining in each participant after IM administration. The predicted efficacious Cmax, based on limited nonclinical studies, is 16-18 ng/mL. At the end of each cohort, the PI, DSMB, and sponsor will evaluate the safety outcomes and PK data associated with the Scopolamine HBT dosing for that group. | 30 Days (+7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scopolamine