Atropine BioequivalencePhase 1SABERNCT06366087
Sublingual Atropine Bioequivalence by Route of Administration (SABER)
A Phase 1 study testing Atropine Sulfate Ophthalmic Solution USP, 1% and Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL) in people with Atropine Bioequivalence, run by Biomedical Advanced Research and Development Authority at 1 site in United States.
Trial summary
A randomized, two-period, two-sequence, crossover study to assess the bioequivalence, bioavailability, and pharmacokinetics (PK) of a single dose of atropine administered sublingually (SL) or intramuscularly (IM) in healthy adult volunteers. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Atropine Bioequivalence
- What is being tested?
- Atropine Sulfate Ophthalmic Solution USP, 1% and Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2024to 22 May 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male and non-pregnant female volunteers between the ages of 18 and 65 years, inclusive, at time of consent.
- Willing and able to provide written informed consent.
- Females who are of childbearing potential and are sexually active with a male partner must have used an adequate method of birth control for at least 2 months prior to Screening and must agree to continue using an adequate method of birth control from Screening through Follow-up (Day 15).
- A female of childbearing potential is defined as a post onset of menarche and premenopausal female capable of becoming pregnant. This does not include females who meet any of the following conditions: menopausal >2 years, tubal ligation >1 year, bilateral salpingo-oophorectomy, or hysterectomy.
- Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label. Examples include oral contraceptives, injectable progestogen, implants of etonogestrel or levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device or intrauterine system, or male partner sterilization at least 6 months prior to the participant's Screening Visit.
- In the judgment of the investigator, the participant is in good health, based on review of medical history and the results of Screening evaluation (including vital signs, physical examination, 12-lead electrocardiogram [ECG], and Screening laboratory assessments, performed no more than 14 days prior to randomization into the study).
- Able to comply with the dosing instructions and available to complete the study Schedule of Assessments.
Who cannot join
- Females who have a positive pregnancy test or who are breastfeeding.
- Participants with thyroid disease as evidenced by a thyroid-stimulating hormone (TSH) <0.9 × lower limit of normal (LLN) or > 1.2 × upper limit of normal (ULN) at Screening (This Screening test will not be repeated prior to subsequent dosing).
- Participants with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or serum creatinine >1.5 × ULN at Screening. (These Screening tests will not be repeated prior to subsequent dosing.)
- Have known human immunodeficiency virus (HIV), or acute or chronic hepatitis B or hepatitis C infection based on medical history; or test positive for any of these at Screening. Participants who have been effectively treated for hepatitis C, as evidenced by a negative hepatitis C RNA confirmation test and who no longer require antiviral therapy, are eligible for participation. (These Screening tests will not be repeated prior to subsequent dosing.)
- Participants who took any prescription medications (with the exception of oral contraceptives or hormone replacement therapy) within 30 days of Screening. Prior to each dose, the investigator will review prohibited medication use and determine whether the participant should be terminated from further dosing.
- Participants who took any over-the-counter medication/vitamins/herbal supplements in the last 72 hours prior to Screening. Prior to each dose, the investigator will review prohibited medication use and determine whether the participant should be terminated from further dosing.
Show all 20Show fewer
- Participants who are current smokers or are currently using any oral nicotine/oral tobacco product (e.g. snuff, chew, lozenges, nicotine gum, pouches) or electronic cigarette or vaping device (e.g., e-cigarette, mod, vape pen, JUUL, e-cigar, e-hookah, e-pipe, vape pods) or have used any of these products within 6 months prior to Screening.
- Participants with glaucoma and/or history of ocular surgery (including LasikTM), ocular trauma, or congenital ocular disorder.
- Participants with any history of heart disease, including but not limited to hypertension, coronary artery disease, arrhythmia (treated or untreated), congestive heart failure, pacemaker, history of vasovagal syncope, any supraventricular tachycardia, peripheral vascular disease, or claudication.
- Participants with clinically significant arrhythmias or abnormal conduction; abnormal conduction is defined as a prolonged PR or QRS, or a QTc ≥450 msec for males or ≥470 msec for females.
- Participants with a history of partial organic pyloric stenosis, chronic constipation, gastroparesis, or other gastrointestinal motility issues.
- Participants with a history of xerostomia due to an underlying disease or previous radiation therapy to the head and neck.
- Males with history of symptomatic prostatic hypertrophy; males or females with a history of urinary hesitancy or retention.
- Participants with a blood pressure >140/90 mm Hg taken after the participant has been seated and resting for at least five minutes.
- Participants with a history or current diagnosis of myasthenia gravis.
- Participants who have donated blood within 8 weeks of Screening or intend to donate blood during the study period.
- Participants with a history of drug or alcohol abuse in the last two years or evidence of a positive urine drug test at Screening. (This Screening test will not be repeated prior to subsequent dosing.)
- Participants with a known sensitivity or prior adverse reaction to atropine.
- Participants who have consumed alcohol within 24 hours prior to each Pre-dose Visit. (This will be assessed only at Visit 1 [Pre-dose] and Visit 2 [Pre-dose].)
- Participants with any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled, would interfere with SL or IM administration of study drug, or would otherwise interfere with interpretation of study results.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johnson County Clin-Trials (JCCT)
Lenexa, Kansas, 66219
About this study
Official title: A Two-Period, Two-Sequence, Two-Treatment, Single-Dose Crossover Study of Atropine Sulfate Ophthalmic Solution (1%) Administered Sublingually vs Atropine Sulfate Administered Intramuscularly for Bioequivalence Determination
A randomized, two-period, two-sequence, crossover study to assess the bioequivalence, bioavailability, and pharmacokinetics (PK) of a single dose of atropine administered sublingually (SL) or intramuscularly (IM) in healthy adult volunteers.
Read the detailed description
This is a randomized, two-period, two-sequence, crossover study to assess the bioequivalence, bioavailability, and pharmacokinetics (PK) of a single dose of atropine administered SL or IM in healthy adult volunteers. A total of 46 healthy male and non-pregnant female volunteers will be randomized, with the goal of obtaining at least 36 evaluable participants in the per protocol population. Additional participants may be randomized if participants are withdrawn prior to receiving one or both doses of study drug. Eligible participants will be randomized at a 1:1 ratio to receive one of two treatment dosing sequences (A [Visit 1 SL, Visit 2 IM] or B [Visit 1 IM, Visit 2 SL]).
Volunteers will be screened for study participation from Days -14 to -3. Eligible participants will be enrolled and randomized to receive one of two dosing sequences (Sequence A or Sequence B) until the target enrollment for the study is met. Once randomized, each participant will receive 2 doses of atropine separated by a wash out period of 6 ±1 days. During Visit 1 (Day 1) and Visit 2 (Day 8), participants will be administered SL or IM atropine, according to their randomly assigned dosing sequence. At each dosing visit, blood samples for PK will be collected at time 0 (pre-dose) and at 13 time points post-dose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes and 2, 2.5, 4, 6, and 8 hours after dosing. Participants will be discharged from the clinic after the 8-hour blood sample collection. Participants will be followed for approximately 6 days after their last dose.
- Conditions
- Atropine Bioequivalence
- Being tested
- Atropine Sulfate Ophthalmic Solution USP, 1%, Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL)
- Keywords
- Pharmaceutical Solutions, Adjuvants, Anesthesia, Anti-Arrhythmia Agents, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Mydriatics, Parasympatholytics, Muscarinic Antagonists, Cholinergic Antagonists, Cholinergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Atropine, Ophthalmic Solutions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atropine Sulfate Ophthalmic Solution USP, 1%Drug
Atropine Sulfate Ophthalmic Solution, USP 1% manufactured by Bausch \& Lomb Americas Inc., is a sterile topical anti-muscarinic indicated for mydriasis, cycloplegia, and penalization of the healthy eye to treat amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains the active ingredient atropine sulfate 10 mg, equivalent to 8.3 mg of atropine. Inactive ingredients are boric acid, hydroxypropyl methylcellulose, and water for injection, USP; hydrochloric acid and/or sodium hydroxide may be added to adjust pH (3.5 to 6.0). Atropine Sulfate Ophthalmic Solution, USP 1% will be supplied in 0.4 mL single-dose vials and will be administered as a single dose to a single participant. 100 μL of Atropine Sulfate Ophthalmic Solution, USP 1% will be given sublingually by pipette to deliver 1.0 mg of atropine sulfate. Before administration, participants will be told to swallow. Once given, participants will be told to try not to swallow for 30 seconds and then swallow normally.
Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL)Drug
Atropine sulfate injection, USP is a muscarinic antagonist used for temporary blockade of severe/life-threatening muscarinic effects and to treat symptomatic bradycardia. Atropine Sulfate Injection, USP, 8 mg/20 mL (0.4 mg/mL) manufactured by Fresenius Kabi is a sterile, nonpyrogenic, isotonic, clear solution of atropine sulfate in water for injection with sodium chloride sufficient to render the solution isotonic. Each mL contains atropine sulfate, 0.4 mg; benzyl alcohol, 9 mg; and sodium chloride 9 mg; it may also contain sulfuric acid for pH adjustment, pH 3.5 (3.0 to 3.8). Atropine Sulfate Injection, USP will be supplied in 8 mg/20 mL multidose vials (0.4 mg/mL). Each vial will be used to administer multiple doses to multiple participants. 2.5 mL will be injected into the mid-anterolateral thigh to deliver 1.0 mg of atropine sulfate. Vials will be dated/timed and will not be given after 24 hours of first entry.
| Study group | Role | What they receive |
|---|---|---|
| Sublingual | Experimental | 1 mg (100 µL of a 1% w/v solution), administered SL by pipette with at least a 30 second dwell time without swallowing. Receives: Drug: Atropine Sulfate Ophthalmic Solution USP, 1% |
| Intramuscular | Active comparator | Multidose vial presentation, 1 mg (2.5 ml) administered by IM injection into the mid-anterolateral thigh. Receives: Drug: Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Infinity (AUCinf).
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCinf is summarized by route of administration 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. Bioequivalence will be considered met if the 90% CI of the ratio for AUCinf lies within 80.00 to 125.00%.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time of Last Quantifiable Data Point (AUCt).
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCt is summarized by route of administration 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. Bioequivalence will be considered met if the 90% CI of the ratio for AUCt lies within 80.00 to 125.00%.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
Secondary outcomes (13)
AUC45 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 45 Minutes (AUC45)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
AUC45 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model
Measured: 0 hour (pre-dose), 5, 10, 15, 20, 30, and 45 minutes post-dose on Days 1 and 8
AUC60 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 60 Minutes (AUC60)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
AUC60 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Measured: 0 hour (pre-dose), 5, 10, 15, 20, 30, 45, and 60 minutes post-dose at Days 1 and 8
AUC90 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 90 (AUC90)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
AUC90 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Measured: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, and 90 minutes post-dose at Days 1 and 8
AUC120 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 120 Minutes (AUC120)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
AUC120 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Measured: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes post-dose at Days 1 and 8
AUC150 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 150 Minutes (AUC150)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
AUC150 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Measured: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, and 150 minutes post-dose at Days 1 and 8
AUC240 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 240 Minutes (AUC240)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
AUC240 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.
Measured: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, and 240 minutes post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Maximum Measured Plasma Concentration (Cmax)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
Cmax is summarized by route of administration 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.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Time to Cmax (Tmax)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
tmax is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as minutes.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Apparent Terminal Elimination Half-life (t1/2)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
t1/2 is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as minutes.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Terminal Elimination Rate Constant (λz)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
λz is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as 1/min.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Volume of Distribution (Vd/F)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
Vd/F is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as mL.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Total Body Clearance (CL/F)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
CL/F is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as mL/min.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Absorption Rate Constant (Ka)
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods.
Ka is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed 1/min.
Measured: Pre-dose through 8 hours post-dose at Days 1 and 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2024
- Study start15 Apr 2024
- Primary completion15 May 2024
- Study completion22 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Atropine BioequivalenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biomedical Advanced Research and Development Authority
- Sponsor type
- US federal agency
- Collaborators
- Rho Federal Systems Division, Inc., Allucent Government Services (US), LLC
- Responsible party
- Sponsor
- Investigators
- Derek Eisnor, MD, Study chair, Biomedical Advanced Research and Development AuthorityMichael Schwartz, MD, Study chair, Biomedical Advanced Research and Development Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06366087
- Sponsor's protocol ID
- BP-C-24-001
- Acronym
- SABER
- Status last verified
- Jan 2026
- First submitted
- 11 Apr 2024
- Last updated
- 27 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Period, Two-Sequence, Two-Treatment, Single-Dose Crossover Study of Atropine Sulfate Ophthalmic Solution (1%) Administered Sublingually vs Atropine Sulfate Administered Intramuscularly for Bioequivalence Determination
- ClinicalTrials.gov ID
- NCT06366087
- Acronym / sponsor ID
- SABER / BP-C-24-001
- Conditions
- Atropine Bioequivalence
- Keywords
- Pharmaceutical Solutions, Adjuvants, Anesthesia, Anti-Arrhythmia Agents, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Biomedical Advanced Research and Development AuthorityUS federal agency
- Collaborators
- Rho Federal Systems Division, Inc., Allucent Government Services (US), LLC
- Study start
- 15 Apr 2024 (actual)
- Primary completion
- 15 May 2024 (actual)
- Study completion
- 22 May 2024 (actual)
- First posted
- 15 Apr 2024 (actual)
- Results
- Posted 4 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, two-period, two-sequence, crossover study to assess the bioequivalence, bioavailability, and pharmacokinetics (PK) of a single dose of atropine administered sublingually (SL) or intramuscularly (IM) in healthy adult volunteers.
Detailed description
This is a randomized, two-period, two-sequence, crossover study to assess the bioequivalence, bioavailability, and pharmacokinetics (PK) of a single dose of atropine administered SL or IM in healthy adult volunteers. A total of 46 healthy male and non-pregnant female volunteers will be randomized, with the goal of obtaining at least 36 evaluable participants in the per protocol population. Additional participants may be randomized if participants are withdrawn prior to receiving one or both doses of study drug. Eligible participants will be randomized at a 1:1 ratio to receive one of two treatment dosing sequences (A [Visit 1 SL, Visit 2 IM] or B [Visit 1 IM, Visit 2 SL]).
Volunteers will be screened for study participation from Days -14 to -3. Eligible participants will be enrolled and randomized to receive one of two dosing sequences (Sequence A or Sequence B) until the target enrollment for the study is met. Once randomized, each participant will receive 2 doses of atropine separated by a wash out period of 6 ±1 days. During Visit 1 (Day 1) and Visit 2 (Day 8), participants will be administered SL or IM atropine, according to their randomly assigned dosing sequence. At each dosing visit, blood samples for PK will be collected at time 0 (pre-dose) and at 13 time points post-dose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes and 2, 2.5, 4, 6, and 8 hours after dosing. Participants will be discharged from the clinic after the 8-hour blood sample collection. Participants will be followed for approximately 6 days after their last dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sublingual | Experimental | Drug: Atropine Sulfate Ophthalmic Solution USP, 1%1 mg (100 µL of a 1% w/v solution), administered SL by pipette with at least a 30 second dwell time without swallowing. |
| Intramuscular | Active comparator | Drug: Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL)Multidose vial presentation, 1 mg (2.5 ml) administered by IM injection into the mid-anterolateral thigh. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Healthy male and non-pregnant female volunteers between the ages of 18 and 65 years, inclusive, at time of consent.
- Willing and able to provide written informed consent.
- Females who are of childbearing potential and are sexually active with a male partner must have used an adequate method of birth control for at least 2 months prior to Screening and must agree to continue using an adequate method of birth control from Screening through Follow-up (Day 15).
- In the judgment of the investigator, the participant is in good health, based on review of medical history and the results of Screening evaluation (including vital signs, physical examination, 12-lead electrocardiogram [ECG], and Screening laboratory assessments, performed no more than 14 days prior to randomization into the study).
- Able to comply with the dosing instructions and available to complete the study Schedule of Assessments.
Key exclusion criteria (20 listed)
- Females who have a positive pregnancy test or who are breastfeeding.
- Participants with thyroid disease as evidenced by a thyroid-stimulating hormone (TSH) <0.9 × lower limit of normal (LLN) or > 1.2 × upper limit of normal (ULN) at Screening (This Screening test will not be repeated prior to subsequent dosing).
- Participants with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or serum creatinine >1.5 × ULN at Screening. (These Screening tests will not be repeated prior to subsequent dosing.)
- Have known human immunodeficiency virus (HIV), or acute or chronic hepatitis B or hepatitis C infection based on medical history; or test positive for any of these at Screening. Participants who have been effectively treated for hepatitis C, as evidenced by a negative hepatitis C RNA confirmation test and who no longer require antiviral therapy, are eligible for participation. (These Screening tests will not be repeated prior to subsequent dosing.)
- Participants who took any prescription medications (with the exception of oral contraceptives or hormone replacement therapy) within 30 days of Screening. Prior to each dose, the investigator will review prohibited medication use and determine whether the participant should be terminated from further dosing.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atropine Sulfate Ophthalmic Solution USP, 1%Atropine Sulfate Ophthalmic Solution, USP 1% manufactured by Bausch \& Lomb Americas Inc., is a sterile topical anti-muscarinic indicated for mydriasis, cycloplegia, and penalization of the healthy eye to treat amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains the active ingredient atropine sulfate 10 mg, equivalent to 8.3 mg of atropine. Inactive ingredients are boric acid, hydroxypropyl methylcellulose, and water for injection, USP; hydrochloric acid and/or sodium hydroxide may be added to adjust pH (3.5 to 6.0). Atropine Sulfate Ophthalmic Solution, USP 1% will be supplied in 0.4 mL single-dose vials and will be administered as a single dose to a single participant. 100 μL of Atropine Sulfate Ophthalmic Solution, USP 1% will be given sublingually by pipette to deliver 1.0 mg of atropine sulfate. Before administration, participants will be told to swallow. Once given, participants will be told to try not to swallow for 30 seconds and then swallow normally. | Drug | Sublingual |
| Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL)Atropine sulfate injection, USP is a muscarinic antagonist used for temporary blockade of severe/life-threatening muscarinic effects and to treat symptomatic bradycardia. Atropine Sulfate Injection, USP, 8 mg/20 mL (0.4 mg/mL) manufactured by Fresenius Kabi is a sterile, nonpyrogenic, isotonic, clear solution of atropine sulfate in water for injection with sodium chloride sufficient to render the solution isotonic. Each mL contains atropine sulfate, 0.4 mg; benzyl alcohol, 9 mg; and sodium chloride 9 mg; it may also contain sulfuric acid for pH adjustment, pH 3.5 (3.0 to 3.8). Atropine Sulfate Injection, USP will be supplied in 8 mg/20 mL multidose vials (0.4 mg/mL). Each vial will be used to administer multiple doses to multiple participants. 2.5 mL will be injected into the mid-anterolateral thigh to deliver 1.0 mg of atropine sulfate. Vials will be dated/timed and will not be given after 24 hours of first entry. | Drug | Intramuscular |
Primary outcome
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Infinity (AUCinf).
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCinf is summarized by route of administration 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. Bioequivalence will be considered met if the 90% CI of the ratio for AUCinf lies within 80.00 to 125.00%.
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time of Last Quantifiable Data Point (AUCt).
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCt is summarized by route of administration 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. Bioequivalence will be considered met if the 90% CI of the ratio for AUCt lies within 80.00 to 125.00%.
13 secondary outcomes
AUC45 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 45 Minutes (AUC45)
Time frame: 0 hour (pre-dose), 5, 10, 15, 20, 30, and 45 minutes post-dose on Days 1 and 8
AUC60 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 60 Minutes (AUC60)
Time frame: 0 hour (pre-dose), 5, 10, 15, 20, 30, 45, and 60 minutes post-dose at Days 1 and 8
AUC90 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 90 (AUC90)
Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, and 90 minutes post-dose at Days 1 and 8
AUC120 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 120 Minutes (AUC120)
Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes post-dose at Days 1 and 8
AUC150 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 150 Minutes (AUC150)
Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, and 150 minutes post-dose at Days 1 and 8
AUC240 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 240 Minutes (AUC240)
Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, and 240 minutes post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Maximum Measured Plasma Concentration (Cmax)
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Time to Cmax (Tmax)
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Apparent Terminal Elimination Half-life (t1/2)
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Terminal Elimination Rate Constant (λz)
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Volume of Distribution (Vd/F)
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Total Body Clearance (CL/F)
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Absorption Rate Constant (Ka)
Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Derek Eisnor, MD study chair
Biomedical Advanced Research and Development Authority
Michael Schwartz, MD study chair
Biomedical Advanced Research and Development Authority
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atropine Sulfate Ophthalmic Solution USP, 1% and Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL) in people with Atropine Bioequivalence, run by Biomedical Advanced Research and Development Authority at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Infinity (AUCinf). (time frame: Pre-dose through 8 hours post-dose at Days 1 and 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.