- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02447315
A Study to Investigate the Effect of Oral Doses of Pilocarpine on Salivary Secretion and Static Pupillometry in Healthy Subjects
August 10, 2015 updated by: Astellas Pharma Europe B.V.
A Phase 1 Study to Investigate the Effect of Oral Doses of Pilocarpine on Salivary Secretion and Static Pupillometry in Healthy Subjects
The purpose of this study is to evaluate the pharmacodynamic effect of oral doses of pilocarpine on salivary secretion in healthy male and female subjects.
In addition, pharmacodynamic effect on static pupillometry will be evaluated as well as pharmacokinetics and safety and tolerability of oral doses of pilocarpine in healthy subjects.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
12
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Harrow, United Kingdom, HA1 3UJ
- PAREXEL Early Phase Clinical Unit
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Subject has a body mass index range of 18.5 to 30.0 kg/m2, inclusive. The subject weighs at least 50 kg. [screening]
Female subject must either:
Be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
- Documented surgically sterile.
Or, if of childbearing potential:
- Agree not to try to become pregnant during the clinical study and for 28 days after the final study drug administration,
- Must have a negative serum pregnancy test at day -1,
- And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control (at least 1 of which must be a barrier method) starting at screening and throughout the clinical study period after the final study drug administration. Highly effective forms of birth control include: Consistent and correct usage of established oral contraception; Injected or implanted hormonal methods of contraception; Established intrauterine device or intrauterine system; Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Female subject must agree not to breastfeed starting at screening and throughout the clinical study period, and for 28 days after the final study drug administration.
- Female subject must not donate ova starting at screening and throughout the clinical study period, and for 28 days after the final study drug administration.
- Male subject must not donate sperm starting at screening and throughout the clinical study period, and for 90 days after last study drug administration.
- Subject agrees not to participate in another interventional study while participation in the present clinical study, defined as signing the informed consent form until completion of the last study visit.
Exclusion Criteria:
- Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
- Subject has a known or suspected hypersensitivity to pilocarpine or any components of the formulation used.
- Subject has clinically significant, uncontrolled cardiorenal disease, uncontrolled asthma, chronic obstructive pulmonary disease, cholelithiasis, urolithiasis, current or previous peptic ulcer disease and/or any other chronic disease at risk for cholinergic agonists.
- Subject has a condition of the eye which could be affected by the intake of pilocarpine (e.g., acute iritis).
- Subject has any of the liver chemistry tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma glutamyl transferase, total bilirubin [TBL]) above 1.5 × the upper limit of normal (ULN). In such a case, the assessment may be repeated once, on day -1.
- Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy.
- Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to admission to the clinical unit (day -1).
- Subject has any clinically significant abnormality of the physical examination, ECG and clinical study protocol-defined clinical laboratory tests at screening or day -1.
- Subject has a mean pulse < 50 or > 90 bpm; mean systolic BP > 140 mmHg; mean diastolic BP > 90 mmHg (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) on admission to the clinical unit (day -1). If the mean BP exceeds the limits above, 1 additional triplicate can be taken.
- Subject has a mean corrected QT interval using Fridericia's formula (QTcF) > 430 ms (for male subjects) and > 450 ms (for female subjects) at screening. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken on day -1.
- Subject uses any prescribed or nonprescribed drugs (including Salagen tablets or pilocarpine-containing eye drops in the month prior to first study drug administration / vitamins, natural and herbal remedies [e.g., St. John's wort] in the 2 weeks prior to first study drug administration) except for occasional use of paracetamol (up to 2 g/day) and except for use of contraceptives or hormone replacement therapy.
- Subject has a history of smoking within 1 month prior to first study drug administration (day 1).
- Subject has a history of drinking > 21 units of alcohol/week for male subjects or > 14 units of alcohol/week for female subjects (1 unit = 10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) within 3 months prior to admission to the clinical unit (day -1).
- Subject has consumed grapefruit or Seville oranges or grapefruit- / Seville orange-containing products within 72 hours prior to admission to the clinical unit (day -1).
- Subject uses any inducer of metabolism (e.g., barbiturates, rifampin) within 1 month prior to admission to the clinical unit (day -1).
- Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit (day -1).
- Subject had significant blood loss, donated 1 unit (500 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to admission to the clinical unit (day -1).
- Subject has a positive serology test for hepatitis B surface antigen, hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies, or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at screening.
- Subject participated in any clinical study or has been treated with any investigational drugs within 28 days prior to screening.
- Subject is an employee of the Astellas Group or Contract Research Organization (CRO).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment Sequence ABCDD
Subjects receive a single dose out of 4 oral doses of study drug (pilocarpine or matching placebo) per day for 5 subsequent days in the sequence ABCDD.
Treatment A: pilocarpine low dose, Treatment B: pilocarpine medium dose, Treatment C: pilocarpine high dose, Treatment D: Placebo
|
oral
oral
Other Names:
|
Experimental: Treatment Sequence BDACC
Subjects receive a single dose out of 4 oral doses of study drug (pilocarpine or matching placebo) per day for 5 subsequent days in the sequence BDACC.
Treatment A: pilocarpine low dose, Treatment B: pilocarpine medium dose, Treatment C: pilocarpine high dose, Treatment D: Placebo
|
oral
oral
Other Names:
|
Experimental: Treatment Sequence CADBB
Subjects receive a single dose out of 4 oral doses of study drug (pilocarpine or matching placebo) per day for 5 subsequent days in the sequence CADBB.
Treatment A: pilocarpine low dose, Treatment B: pilocarpine medium dose, Treatment C: pilocarpine high dose, Treatment D: Placebo
|
oral
oral
Other Names:
|
Experimental: Treatment Sequence DCBAA
Subjects receive a single dose out of 4 oral doses of study drug (pilocarpine or matching placebo) per day for 5 subsequent days in the sequence DCBAA.
Treatment A: pilocarpine low dose, Treatment B: pilocarpine medium dose, Treatment C: pilocarpine high dose, Treatment D: Placebo
|
oral
oral
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacodynamic parameter salivary secretion at specified time points
Time Frame: Days 1-5
|
Measure (mg/min) salivary secretion at specific timepoints
|
Days 1-5
|
Pharmacodynamics assessed by area under the effect-time curve (AUE), saliva (AUEsal)
Time Frame: Days 1-5
|
Days 1-5
|
|
Pharmacodynamics assessed by maximal effect (Emax), saliva (Emax, sal)
Time Frame: Days 1-5
|
Days 1-5
|
|
Pharmacodynamics assessed by time at which the maximum salivary flow occurs (tmax, sal)
Time Frame: Days 1-5
|
Days 1-5
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacodynamic profile pupil diameter pupS, pupLM, pupHM, AUEpupS, AUEpupLM, AUEpupHM, Emax,pupS, Emax,pupLM, Emax,pupHM, tmax,pupS, tmax,pupLM, tmax,pupHM
Time Frame: Days 1-5
|
Pupil diameter, scotopic lighting condition (pupS); Pupil diameter, low mesopic lighting condition (pupLM); Pupil diameter, high mesopic lighting condition (pupHM); Area under the effect curve pupil diameter, scotopic lighting condition (AUEpupS); Area under the effect curve pupil diameter, low mesopic lighting condition (AUEpupLM); Area under the effect curve pupil diameter, high mesopic lighting condition (AUEpupHM); Maximum pharmacodynamic effect pupil diameter, scotopic lighting condition (Emax,pupS); Maximum pharmacodynamic effect pupil diameter, low mesopic lighting condition (Emax,pupLM); Maximum pharmacodynamic effect pupil diameter, high mesopic lighting condition (Emax,pupHM), Time at maximum concentration pupil diameter, scotopic lighting condition (tmax,pupS); Time at maximum concentration pupil diameter, low mesopic lighting condition (tmax,pupLM), Time at maximum concentration pupil diameter, high mesopic lighting condition (tmax,pupHM)
|
Days 1-5
|
Safety profile assessed by adverse events, vital signs, routine electrocardiograms (ECG) , and clinical laboratory tests
Time Frame: up to Day 14
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Vital signs include body temperature, blood pressure and pulse.
Clinical laboratory test include hematology, biochemistry and urinalysis.
|
up to Day 14
|
Pharmacokinetics profile of pilocarpine: maximum concentration (Cmax), time of maximum concentration (tmax) and area under the concentration-time curve from the time of dosing (time zero) to 6 hours (AUC6)
Time Frame: Days 1-5
|
Days 1-5
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Associate Medical Director, Astellas Pharma Europe B.V.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2015
Primary Completion (Actual)
June 1, 2015
Study Completion (Actual)
June 1, 2015
Study Registration Dates
First Submitted
March 31, 2015
First Submitted That Met QC Criteria
May 14, 2015
First Posted (Estimate)
May 18, 2015
Study Record Updates
Last Update Posted (Estimate)
August 13, 2015
Last Update Submitted That Met QC Criteria
August 10, 2015
Last Verified
August 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TRAN-CL-0004
- 2014-004753-13 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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