Medical Countermeasures, Organophosphate Poisoning
Conditions
Keywords
Scopolamine
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
Detailed description
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.
Interventions
DRUGScopolamine Hydrobromide Trihydrate
Scopolamine Hydrobromide Trihydrate Intramuscular Injection
Sponsors
Battelle Memorial Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
double-blinded, randomized, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female, 18 to 55 years of age, inclusive, at the time of drug administration 2. Without clinically significant abnormities on physical examination at screening or prior to drug administration 3. Generally healthy, as determined by medical history review, physical examination, and laboratory testing at screening and prior to drug administration 4. 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 5. Must have adequate venous access and sufficient upper leg muscle tissue for drug administration 6. If female, the subject must be nonpregnant and nonbreastfeeding, and have a negative serum pregnancy test at screening and prior to drug administration 7. 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 8. 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) 9. 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 10. 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) 11. 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 12. 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) 13. 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) 14. Ability to read, speak, and comprehend English and a willingness to sign informed consent
Exclusion criteria
1. Received any other investigational drug within 30 days prior to drug administration 2. Known allergies to any component of the study drug, other belladonna alkaloids, or the recovery medications (physostigmine, atropine, or benzodiazepines \[diazepam or lorazepam\]) 3. History of migraine headaches or seizures 4. History of psychosis or psychotic episodes 5. 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 6. 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 7. Has consumed Seville orange (bitter orange), grapefruit, grapefruit juice, other grapefruit-containing products, or starfruit within 7 days prior to dosing 8. Has consumed caffeine or other xanthine-containing products within 7 days prior to dosing 9. 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 10. Has positive (reactive) test results for hepatitis B surface antigen, hepatitis C, syphilis, HIV-1, or HIV-2 11. Has narrow-angle glaucoma or high intraocular pressures in either or both eyes 12. Has pyloric obstruction or urinary bladder neck obstruction 13. Has impaired liver or kidney functions 14. Clinically relevant electrocardiogram (ECG) abnormalities on any 12-lead ECG obtained at screening or prior to dosing 15. ECG with a PR interval ≥ 200 msec at screening or prior to dosing 16. ECG with QRS duration \> 120 msec at screening or prior to dosing 17. ECG RR interval \> 1500 msec at screening or prior to dosing 18. 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 19. Systolic blood pressure \> 140 mm Hg and/or diastolic blood pressure \> 90 mm Hg at screening or prior to dosing 20. Systolic blood pressure \< 90 mm Hg and/or diastolic blood pressure \< 50 mm Hg at screening or prior to dosing 21. 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 22. 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) 23. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Degree and Number of Adverse Events Experienced by Subjects. | 30 Days (+7) | Safety and tolerability profile of ascending doses of scopolamine hydrobromide trihydrate (Scopolamine HBT) administered by intramuscular (IM) injection |
| Cmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 30 Days (+7) | Cmax of ascending doses of Scopolamine HBT administered by IM injection. |
| Tmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 30 Days (+7) | Tmax 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) | Apparent Volume of Distribution (mL/kg) 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) | t1/2 (hr) 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) | Apparent Clearance (mL/hr/kg) 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) | MRT (hr) 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) | AUClast (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) | AUCinfinity (hr\*ug/mL) 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) | Cmax/Dose (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) | AUCinfinity/Dose (hr\*ug/mL)/(mg/kg) of ascending doses of Scopolamine HBT administered by IM injection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg Dose of Scopolamine 0.005mg/kg verses Placebo
Scopolamine Hydrobromide Trihydrate: Scopolamine Hydrobromide Trihydrate Intramuscular Injection | 6 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg Dose of Scopolamine 0.007mg/kg verses Placebo
Scopolamine Hydrobromide Trihydrate: Scopolamine Hydrobromide Trihydrate Intramuscular Injection | 6 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg Dose of Scopolamine 0.011mg/kg verses Placebo
Scopolamine Hydrobromide Trihydrate: Scopolamine Hydrobromide Trihydrate Intramuscular Injection | 6 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg Dose of Scopolamine 0.014mg/kg verses Placebo
Scopolamine Hydrobromide Trihydrate: Scopolamine Hydrobromide Trihydrate Intramuscular Injection | 6 |
| Cohort 5 Scopolamine HBT 0.021 mg/kg Dose of Scopolamine 0.021mg/kg verses Placebo
Scopolamine Hydrobromide Trihydrate: Scopolamine Hydrobromide Trihydrate Intramuscular Injection | 0 |
| Placebo Placebo controlled | 8 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1 Scopolamine HBT 0.005 mg/kg | Cohort 2 Scopolamine HBT 0.007 mg/kg | Cohort 3 Scopolamine HBT 0.011 mg/kg | Cohort 4 Scopolamine HBT 0.014 mg/kg | Placebo | Cohort 5 Scopolamine HBT 0.021 mg/kg |
|---|---|---|---|---|---|---|---|
| Age, Customized Age (years) mean | 33.8 years STANDARD_DEVIATION 9.58 | 34.8 years STANDARD_DEVIATION 9.6 | 34.8 years STANDARD_DEVIATION 9.11 | 31.7 years STANDARD_DEVIATION 10.31 | 35.7 years STANDARD_DEVIATION 11.48 | 32.6 years STANDARD_DEVIATION 10.07 | — |
| Body Mass Index (BMI) | 24.94 kg/m^2 STANDARD_DEVIATION 2.442 | 24.55 kg/m^2 STANDARD_DEVIATION 3.454 | 25.58 kg/m^2 STANDARD_DEVIATION 2.143 | 24.17 kg/m^2 STANDARD_DEVIATION 1.876 | 25.95 kg/m^2 STANDARD_DEVIATION 2.669 | 24.58 kg/m^2 STANDARD_DEVIATION 2.232 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 6 Participants | 3 Participants | 5 Participants | 4 Participants | 6 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | — |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Black or African American | 19 Participants | 5 Participants | 2 Participants | 4 Participants | 3 Participants | 5 Participants | — |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | — |
| Region of Enrollment United States | 32 participants | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants | — |
| Sex: Female, Male Female | 15 Participants | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 3 Participants | — |
| Sex: Female, Male Male | 17 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 5 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 8 |
| other Total, other adverse events | 6 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 0 / 0 | 5 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 8 |
Outcome results
Primary
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.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Apparent Clearance (mL/hr/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 2177 Apparent Clearance (mL/hr/kg) | Standard Deviation 545.6 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Apparent Clearance (mL/hr/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 2100 Apparent Clearance (mL/hr/kg) | Standard Deviation 805.2 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Apparent Clearance (mL/hr/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 2012 Apparent Clearance (mL/hr/kg) | Standard Deviation 253.9 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Apparent Clearance (mL/hr/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1765 Apparent Clearance (mL/hr/kg) | Standard Deviation 375.4 |
Primary
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.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Apparent Volume of Distribution (mL/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 6258 Apparent Volume of Distribution (mL/kg) | Standard Deviation 1678.1 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Apparent Volume of Distribution (mL/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 5552 Apparent Volume of Distribution (mL/kg) | Standard Deviation 1710.3 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Apparent Volume of Distribution (mL/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 5963 Apparent Volume of Distribution (mL/kg) | Standard Deviation 970.8 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Apparent Volume of Distribution (mL/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 10210 Apparent Volume of Distribution (mL/kg) | Standard Deviation 4402.5 |
Primary
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.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | AUCinfinity/Dose (hr*ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 481 AUCinfinity/Dose (hr*ug/mL)/(mg/kg) | Standard Deviation 100.3 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | AUCinfinity/Dose (hr*ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 535 AUCinfinity/Dose (hr*ug/mL)/(mg/kg) | Standard Deviation 188.6 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | AUCinfinity/Dose (hr*ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 504 AUCinfinity/Dose (hr*ug/mL)/(mg/kg) | Standard Deviation 62.5 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | AUCinfinity/Dose (hr*ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 590 AUCinfinity/Dose (hr*ug/mL)/(mg/kg) | Standard Deviation 140.4 |
Primary
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.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | AUCinfinity (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 2.4 AUCinfinity (hr*ug/mL) | Standard Deviation 0.5 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | AUCinfinity (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 3.7 AUCinfinity (hr*ug/mL) | Standard Deviation 1.32 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | AUCinfinity (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 5.5 AUCinfinity (hr*ug/mL) | Standard Deviation 0.68 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | AUCinfinity (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 8.3 AUCinfinity (hr*ug/mL) | Standard Deviation 1.98 |
Primary
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.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | AUClast (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 2.36 AUClast (hr*ug/mL) | Standard Deviation 0.499 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | AUClast (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 3.67 AUClast (hr*ug/mL) | Standard Deviation 1.293 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | AUClast (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 5.47 AUClast (hr*ug/mL) | Standard Deviation 0.694 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | AUClast (hr*ug/mL) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 8.16 AUClast (hr*ug/mL) | Standard Deviation 1.94 |
Primary
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.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Cmax/Dose (ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 133 Cmax/Dose (ug/mL)/(mg/kg) | Standard Deviation 57.3 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Cmax/Dose (ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 153 Cmax/Dose (ug/mL)/(mg/kg) | Standard Deviation 75.6 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Cmax/Dose (ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 139 Cmax/Dose (ug/mL)/(mg/kg) | Standard Deviation 45.5 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Cmax/Dose (ug/mL)/(mg/kg) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 137 Cmax/Dose (ug/mL)/(mg/kg) | Standard Deviation 32.5 |
Primary
Cmax of Ascending Doses of Scopolamine HBT Administered by IM Injection.
Cmax of ascending doses of Scopolamine HBT administered by IM injection.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Cmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 0.67 Cmax (ug/mL) | Standard Deviation 0.286 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Cmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1.07 Cmax (ug/mL) | Standard Deviation 0.529 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Cmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1.53 Cmax (ug/mL) | Standard Deviation 0.501 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Cmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1.91 Cmax (ug/mL) | Standard Deviation 0.455 |
Primary
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
Time frame: 30 Days (+7)
Population: On 13 June 2021, following DSMB recommendation and final sponsor decision, the PI was notified of the sponsor's decision to close the study to enrollment and not proceed to Cohort 5 (0.021 mg/kg).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | DLTs | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Headache | 3 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site paraesthesia | 2 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site pain | 1 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dry mouth | 4 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Delirium | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs | 6 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | SAEs | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Serious TEAEs | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Treatment-Related Serious TEAEs | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site hypoaesthesia | 1 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study Drug | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Adverse Events : Subjects with at least 1 AE | 6 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Death | 0 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Somnolence | 2 Participants |
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dizziness | 2 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site paraesthesia | 1 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Adverse Events : Subjects with at least 1 AE | 5 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Delirium | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | SAEs | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs | 5 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site hypoaesthesia | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Serious TEAEs | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | DLTs | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dizziness | 4 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Treatment-Related Serious TEAEs | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Somnolence | 3 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Headache | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Death | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site pain | 2 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study Drug | 0 Participants |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dry mouth | 3 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site pain | 2 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dry mouth | 2 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Treatment-Related Serious TEAEs | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Delirium | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site paraesthesia | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study Drug | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Adverse Events : Subjects with at least 1 AE | 6 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dizziness | 3 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs | 6 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | DLTs | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Headache | 1 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site hypoaesthesia | 1 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Serious TEAEs | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Somnolence | 6 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Death | 0 Participants |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | SAEs | 0 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dizziness | 6 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site pain | 2 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site paraesthesia | 2 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site hypoaesthesia | 2 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dry mouth | 1 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Delirium | 3 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs | 6 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Serious TEAEs | 0 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Treatment-Related Serious TEAEs | 0 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Adverse Events : Subjects with at least 1 AE | 6 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Somnolence | 5 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Headache | 2 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study Drug | 0 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study | 0 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Death | 0 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | SAEs | 0 Participants |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Determine Degree and Number of Adverse Events Experienced by Subjects. | DLTs | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site paraesthesia | 2 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Adverse Events : Subjects with at least 1 AE | 5 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Treatment-Related Serious TEAEs | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any Serious TEAEs | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site pain | 3 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Death | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs | 5 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Delirium | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dry mouth | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | DLTs | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | SAEs | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Injection site hypoaesthesia | 2 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Any TEAEs Leading to Discontinuation of Study Drug | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Dizziness | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Headache | 0 Participants |
| Placebo | Determine Degree and Number of Adverse Events Experienced by Subjects. | Somnolence | 1 Participants |
Primary
MRT (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection.
MRT (hr) of ascending doses of Scopolamine HBT administered by IM injection.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | MRT (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 3.18 MRT (hr) | Standard Deviation 0.647 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | MRT (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 3.02 MRT (hr) | Standard Deviation 0.639 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | MRT (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 3.01 MRT (hr) | Standard Deviation 0.355 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | MRT (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 3.81 MRT (hr) | Standard Deviation 0.802 |
Primary
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.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | t1/2 (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1.99 t1/2 (hr) | Standard Deviation 0.235 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | t1/2 (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1.88 t1/2 (hr) | Standard Deviation 0.207 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | t1/2 (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 2.10 t1/2 (hr) | Standard Deviation 0.535 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | t1/2 (hr) of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 4.47 t1/2 (hr) | Standard Deviation 2.876 |
Primary
Tmax of Ascending Doses of Scopolamine HBT Administered by IM Injection.
Tmax of ascending doses of Scopolamine HBT administered by IM injection.
Time frame: 30 Days (+7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Scopolamine HBT 0.005 mg/kg | Tmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1 Tmax (hr) | Standard Deviation 0.4 |
| Cohort 2 Scopolamine HBT 0.007 mg/kg | Tmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1 Tmax (hr) | Standard Deviation 0.8 |
| Cohort 3 Scopolamine HBT 0.011 mg/kg | Tmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1 Tmax (hr) | Standard Deviation 0.6 |
| Cohort 4 Scopolamine HBT 0.014 mg/kg | Tmax of Ascending Doses of Scopolamine HBT Administered by IM Injection. | 1 Tmax (hr) | Standard Deviation 0.5 |