Trial Outcomes & Findings for Sublingual vs IV Atropine Bioavailability Study (NCT NCT04290039)
NCT ID: NCT04290039
Last Updated: 2023-06-22
Results Overview
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using the noncompartmental method for extravascular (for sublingual doses) or IV infusion routes of administration. AUC\_∞ is summarized by study dosage as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
COMPLETED
PHASE1
15 participants
Pre-dose through 8 hours post-dose at Days 1, 8 and 15
2023-06-22
Participant Flow
Participant milestones
| Measure |
Sequence A: Low Dose Sublingual - High Dose Sublingual - IV
Subjects assigned to treatment dosing sequence A will receive a low dose sublingually at Visit 1; Day 1 (Period 1), a high dose sublingually at Visit 2; Day 8 (Period 2) and an IV dose at Visit 3; Day 15 (Period 3).
|
Sequence B: High Dose Sublingual - IV - Low Dose Sublingual
Subjects assigned to treatment dosing sequence B will receive a high dose sublingually at Visit 1; Day 1 (Period 1), an IV dose at Visit 2; Day 8 (Period 2) and a low dose sublingually at Visit 3; Day 15 (Period 3).
|
Sequence C: IV - Low Dose Sublingual - High Dose Sublingual
Subjects assigned to treatment dosing sequence C will receive an IV dose at Visit 1; Day 1 (Period 1), a low dose sublingually at Visit 2; Day 8 (Period 2), and a high dose sublingually at Visit 3; Day 15 (Period 3).
|
|---|---|---|---|
|
Period 1 (Visit 1; Day 1)
STARTED
|
5
|
5
|
5
|
|
Period 1 (Visit 1; Day 1)
COMPLETED
|
5
|
5
|
5
|
|
Period 1 (Visit 1; Day 1)
NOT COMPLETED
|
0
|
0
|
0
|
|
Period 2 (Visit 2; Day 8)
STARTED
|
5
|
5
|
5
|
|
Period 2 (Visit 2; Day 8)
COMPLETED
|
5
|
5
|
5
|
|
Period 2 (Visit 2; Day 8)
NOT COMPLETED
|
0
|
0
|
0
|
|
Period 3 (Visit 3; Day 15)
STARTED
|
5
|
4
|
5
|
|
Period 3 (Visit 3; Day 15)
COMPLETED
|
5
|
4
|
5
|
|
Period 3 (Visit 3; Day 15)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sublingual vs IV Atropine Bioavailability Study
Baseline characteristics by cohort
| Measure |
B: High Dose Sublingual - IV - Low Dose Sublingual
n=5 Participants
Subjects assigned to treatment dosing sequence B will receive a high dose sublingually at Visit 1; Day 1 (Period 1), an IV dose at Visit 2; Day 8 (Period 2) and a low dose sublingually at Visit 3; Day 15 (Period 3).
|
C: Intravenous (IV)-Low Dose Sublingual-High Dose Sublingual
n=5 Participants
Subjects assigned to treatment dosing sequence C will receive an IV dose at Visit 1; Day 1 (Period 1), a low dose sublingually at Visit 2; Day 8 (Period 2), and a high dose sublingually at Visit 3; Day 15 (Period 3).
|
Total
n=15 Participants
Total of all reporting groups
|
A: Low Dose Sublingual - High Dose Sublingual - IV
n=5 Participants
Subjects assigned to treatment dosing sequence A will receive a low dose sublingually at Visit 1; Day 1 (Period 1), a high dose sublingually at Visit 2; Day 8 (Period 2) and an IV dose at Visit 3; Day 15 (Period 3).
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
5 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
29.2 years
STANDARD_DEVIATION 5.76 • n=107 Participants
|
35.0 years
STANDARD_DEVIATION 3.87 • n=206 Participants
|
33.8 years
STANDARD_DEVIATION 6.47 • n=7 Participants
|
37.2 years
STANDARD_DEVIATION 7.46 • n=99 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
5 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
13 Participants
n=7 Participants
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=107 Participants
|
5 participants
n=206 Participants
|
15 participants
n=7 Participants
|
5 participants
n=99 Participants
|
|
Body Mass Index
|
25.16 kg/m^2
n=107 Participants
|
34.13 kg/m^2
n=206 Participants
|
29.55 kg/m^2
n=7 Participants
|
24.76 kg/m^2
n=99 Participants
|
|
Screening Xerostomia Assessment - Difficulty Swallowing (0-10)
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=107 Participants
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=206 Participants
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=7 Participants
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=99 Participants
|
|
Screening Xerostomia Assessment - Dryness of Lips (0-10)
|
1.6 Scores on a scale
STANDARD_DEVIATION 2.07 • n=107 Participants
|
0.2 Scores on a scale
STANDARD_DEVIATION 0.45 • n=206 Participants
|
0.7 Scores on a scale
STANDARD_DEVIATION 1.33 • n=7 Participants
|
0.4 Scores on a scale
STANDARD_DEVIATION 0.55 • n=99 Participants
|
|
Screening Xerostomia Assessment - Dryness of Tongue (0-10)
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=107 Participants
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=206 Participants
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=7 Participants
|
0 Scores on a scale
STANDARD_DEVIATION 0 • n=99 Participants
|
PRIMARY outcome
Timeframe: Pre-dose through 8 hours post-dose at Days 1, 8 and 15Population: The PK analysis population includes all subjects who were randomized, received at least 1 study drug dose, and have PK samples collected for the applicable period.
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using the noncompartmental method for extravascular (for sublingual doses) or IV infusion routes of administration. AUC\_∞ is summarized by study dosage as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Outcome measures
| Measure |
Low Dose Sublingual
n=11 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Area Under the Curve to From Time Zero to Infinity (AUC_∞)
|
286.396 min*ng/mL
Geometric Coefficient of Variation 26.6
|
493.808 min*ng/mL
Geometric Coefficient of Variation 27.3
|
816.465 min*ng/mL
Geometric Coefficient of Variation 22.0
|
PRIMARY outcome
Timeframe: Pre-dose through 8 hours post-dose at Days 1, 8 and 15Population: The PK analysis population includes all subjects who were randomized, received at least 1 study drug dose, and have PK samples collected for the applicable period.
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using the noncompartmental method for extravascular (for sublingual doses) or IV infusion routes of administration. AUC\_t is summarized by study dosage as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Timepoint (AUC_t)
|
218.195 min*ng/mL
Geometric Coefficient of Variation 20.2
|
408.061 min*ng/mL
Geometric Coefficient of Variation 23.9
|
717.665 min*ng/mL
Geometric Coefficient of Variation 23.2
|
PRIMARY outcome
Timeframe: Pre-dose through 8 hours post-dose at Days 1, 8 and 15Population: The PK analysis population includes all subjects who were randomized, received at least 1 study drug dose, and have PK samples collected for the applicable period.
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using the noncompartmental method for extravascular (for sublingual doses) or IV infusion routes of administration. C\_max is summarized by study dosage as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Maximum Concentration (C_max)
|
0.883 ng/mL
Geometric Coefficient of Variation 27.2
|
1.639 ng/mL
Geometric Coefficient of Variation 30.5
|
18.247 ng/mL
Geometric Coefficient of Variation 66.9
|
PRIMARY outcome
Timeframe: Pre-dose through 8 hours post-dose at Days 1, 8 and 15Population: The PK analysis population includes all subjects who were randomized, received at least 1 study drug dose, and have PK samples collected for the applicable periods for extravascular (sublingual) routes of administration. Note: t\_max was not applicable to intravenous dosing.
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and sublingual dosing period using the noncompartmental method. This outcome is not applicable for the intravenous dosing period. t\_max is summarized by study dosage as the mean and standard deviation for all evaluable participants and expressed as minutes.
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Time to Maximum Concentration (t_max)
|
125.4 Minutes
Standard Deviation 69.81
|
107.1 Minutes
Standard Deviation 47.78
|
—
|
PRIMARY outcome
Timeframe: Pre-dose through 8 hours post-dose at Days 1, 8 and 15Population: The PK analysis population includes all subjects who were randomized, received at least 1 study drug dose, and have PK samples collected for the applicable period.
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using the noncompartmental method for extravascular (for sublingual doses) or IV infusion routes of administration. t\_1/2 is summarized by study dosage as the mean and standard deviation for all evaluable participants and expressed as minutes.
Outcome measures
| Measure |
Low Dose Sublingual
n=11 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Terminal Elimination Half-Life (t_1/2)
|
176.187 Minutes
Standard Deviation 75.0887
|
171.258 Minutes
Standard Deviation 49.9828
|
179.327 Minutes
Standard Deviation 60.412
|
PRIMARY outcome
Timeframe: Pre-dose through 8 hours post-dose at Days 1, 8 and 15Population: The PK analysis population includes all subjects who were randomized, received at least 1 study drug dose, and have PK samples collected for the applicable periods for extravascular (sublingual) routes of administration. Note: V\_d/F is not applicable to intravenous dosing.
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and sublingual dosing period using the noncompartmental method. This outcome is not applicable for the intravenous dosing period. V\_d/F is summarized by study dosage as the mean and standard deviation for all evaluable participants and expressed as liters.
Outcome measures
| Measure |
Low Dose Sublingual
n=11 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Volume of Distribution (V_d/F)
|
423.71 L
Standard Deviation 119.774
|
496.70 L
Standard Deviation 138.811
|
—
|
PRIMARY outcome
Timeframe: Pre-dose through 8 hours post-dose at Days 1, 8 and 15Population: The PK analysis population includes all subjects who were randomized, received at least 1 study drug dose, and have PK samples collected for the applicable periods for extravascular (sublingual) routes of administration. Note: CL/F is not applicable to intravenous dosing.
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 2, 4, 6, 10, 15, 20, 30, 45, and 60 minutes, and 2, 4, 6, and 8 hours. PK parameters were estimated for each subject and sublingual dosing period using the noncompartmental method. This outcome is not applicable for the intravenous dosing period. CL/F is summarized by study dosage as the mean and standard deviation for all evaluable participants and expressed as mL/min.
Outcome measures
| Measure |
Low Dose Sublingual
n=11 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Clearance (CL/F)
|
1800.800 mL/min
Standard Deviation 473.3604
|
2098.806 mL/min
Standard Deviation 632.8211
|
—
|
SECONDARY outcome
Timeframe: Day 1 through Day 21Population: The Safety population includes all subjects who were randomized and received at least 1 study drug dose.
Number of patients with treatment-emergent adverse events
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Treatment-Emergent Adverse Events
|
1 Participants
|
1 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 21Population: The Safety population includes all subjects who were randomized and received at least 1 study drug dose.
Number of patients with treatment-emergent serious adverse events
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Treatment-Emergent Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose through 1 hour post-dose at Days 1, 8 and 15Population: The Safety population includes all subjects who were randomized and received at least 1 study drug dose.
Subject reported xerostomia scores were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 10, 20, 30, 40, 50, and 60 minutes. Scores were assessed by questionnaire (0-10 point scale, with 0 being not difficult at all and 10 being very difficult) previously validated for measurement of salivary gland dysfunction. The maximum xerostomia score representing difficulty swallowing due to mouth dryness was calculated for each subject and dose. Maximum xerostomia scores were summarized by study dosage as the mean and standard deviation.
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Xerostomia Assessment - Difficulty Swallowing Due to Mouth Dryness
|
0.3 Scores on a scale
Standard Deviation 1.07
|
0.3 Scores on a scale
Standard Deviation 0.82
|
2.0 Scores on a scale
Standard Deviation 2.77
|
SECONDARY outcome
Timeframe: Pre-dose through 1 hour post-dose at Days 1, 8 and 15Population: The Safety population includes all subjects who were randomized and received at least 1 study drug dose.
Subject reported xerostomia scores were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 10, 20, 30, 40, 50, and 60 minutes. Scores were assessed by questionnaire (0-10 point scale, with 0 being not dry at all and 10 being very dry) previously validated for measurement of salivary gland dysfunction. The maximum xerostomia score representing dryness of lips was calculated for each subject and dose. Maximum xerostomia scores were summarized by study dosage as the mean and standard deviation.
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Xerostomia Assessment - Dryness of Lips
|
1.1 Maximum Score
Standard Deviation 1.38
|
1.5 Maximum Score
Standard Deviation 1.85
|
2.9 Maximum Score
Standard Deviation 2.88
|
SECONDARY outcome
Timeframe: Pre-dose through 1 hour post-dose at Days 1, 8 and 15Subject reported xerostomia scores were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 10, 20, 30, 40, 50, and 60 minutes. Scores were assessed by questionnaire (0-10 point scale, with 0 being not dry at all and 10 being very dry) previously validated for measurement of salivary gland dysfunction. The maximum xerostomia score representing dryness of tongue was calculated for each subject and dose. Maximum xerostomia scores were summarized by study dosage as the mean and standard deviation.
Outcome measures
| Measure |
Low Dose Sublingual
n=14 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 Participants
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 Participants
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Xerostomia Assessment - Dryness of Tongue
|
0.3 Maximum Score
Standard Deviation 0.61
|
0.3 Maximum Score
Standard Deviation 0.46
|
2.1 Maximum Score
Standard Deviation 2.67
|
Adverse Events
Low Dose Sublingual
High Dose Sublingual
Intravenous
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low Dose Sublingual
n=14 participants at risk
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
High Dose Sublingual
n=15 participants at risk
Atropine sulfate ophthalmic solution, USP 1% is a sterile topical anti-muscarinic indicated for cyclopegia, mydriasis, and penalization of the healthy eye in the treatment of amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains active ingredient: atropine sulfate 10 mg equivalent to 8.3 mg of atropine.
|
Intravenous
n=14 participants at risk
Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain - Lower
|
7.1%
1/14 • Number of events 1 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
0.00%
0/15 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
0.00%
0/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
6.7%
1/15 • Number of events 1 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
0.00%
0/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
0.00%
0/15 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
14.3%
2/14 • Number of events 2 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
0.00%
0/15 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
7.1%
1/14 • Number of events 1 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
|
Nervous system disorders
Headache
|
0.00%
0/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
0.00%
0/15 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
7.1%
1/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
|
Vascular disorders
Flushing
|
0.00%
0/14 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
0.00%
0/15 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
7.1%
1/14 • Number of events 1 • AEs were collected from the time of consent until completion of the follow-up period after the last administration of study drug Follow-up (Day 21).
Events grade 1 or higher were be recorded on the appropriate AE electronic case report form (eCRF) for this study. The study site graded the severity of AEs experienced by the study participants according to the criteria set forth in the NCI-CTCAE Version 5.0.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place