Healthy SubjectsPhase 1NCT02447315

A Study to Investigate the Effect of Oral Doses of Pilocarpine on Salivary Secretion and Static Pupillometry in Healthy Subjects

A Phase 1 study testing Pilocarpine in people with Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Subjects
What is being tested?: Pilocarpine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 12 participants
Where: 1 siteUnited Kingdom
Study dates: May 2015to Jun 2015
Phase: Phase 1
Are there results?: None posted in the registry

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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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:

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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.

Who cannot join

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).

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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).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

PAREXEL Early Phase Clinical Unit
Harrow, HA1 3UJ

Other trials in United Kingdom

About this study

Official title: A Phase 1 Study to Investigate the Effect of Oral Doses of Pilocarpine on Salivary Secretion and Static Pupillometry in Healthy Subjects

Conditions: Healthy Subjects
Being tested: Pilocarpine, Placebo
Keywords: Pilocarpine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PilocarpineDrug
Also called Salagen
oral
PlaceboDrug
oral

Study groups in NCT02447315
Study group	Role	What they receive
Treatment Sequence ABCDD	Experimental	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 Receives: Drug: Pilocarpine; Drug: Placebo
Treatment Sequence BDACC	Experimental	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 Receives: Drug: Pilocarpine; Drug: Placebo
Treatment Sequence CADBB	Experimental	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 Receives: Drug: Pilocarpine; Drug: Placebo
Treatment Sequence DCBAA	Experimental	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 Receives: Drug: Pilocarpine; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacodynamic parameter salivary secretion at specified time points
Measure (mg/min) salivary secretion at specific timepoints
Measured: Days 1-5
Pharmacodynamics assessed by area under the effect-time curve (AUE), saliva (AUEsal)
Measured: Days 1-5
Pharmacodynamics assessed by maximal effect (Emax), saliva (Emax, sal)
Measured: Days 1-5
Pharmacodynamics assessed by time at which the maximum salivary flow occurs (tmax, sal)
Measured: Days 1-5

Secondary outcomes (3)

Pharmacodynamic profile pupil diameter pupS, pupLM, pupHM, AUEpupS, AUEpupLM, AUEpupHM, Emax,pupS, Emax,pupLM, Emax,pupHM, tmax,pupS, tmax,pupLM, tmax,pupHM
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)
Measured: Days 1-5
Safety profile assessed by adverse events, vital signs, routine electrocardiograms (ECG) , and clinical laboratory tests
Vital signs include body temperature, blood pressure and pulse. Clinical laboratory test include hematology, biochemistry and urinalysis.
Measured: 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)
Measured: Days 1-5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2015Jun 2015

First posted18 May 2015 (estimated)
Study startMay 2015
Primary completionJun 2015
Study completionJun 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Healthy SubjectsStudies 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: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02447315
Sponsor's protocol ID: TRAN-CL-0004
Other IDs: 2014-004753-13, 2014
Status last verified: Aug 2015
First submitted: 31 Mar 2015
Last updated: 13 Aug 2015
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study to Investigate the Effect of Oral Doses of Pilocarpine on Salivary Secretion and Static Pupillometry in Healthy Subjects
ClinicalTrials.gov ID: NCT02447315
Acronym / sponsor ID: TRAN-CL-0004
Conditions: Healthy Subjects
Keywords: Pilocarpine
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
Study start: May 2015
Primary completion: Jun 2015 (actual)
Study completion: Jun 2015 (actual)
First posted: 18 May 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Treatment Sequence ABCDD	Experimental	Drug: Pilocarpine, Drug: PlaceboSubjects 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
Treatment Sequence BDACC	Experimental	Drug: Pilocarpine, Drug: PlaceboSubjects 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
Treatment Sequence CADBB	Experimental	Drug: Pilocarpine, Drug: PlaceboSubjects 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
Treatment Sequence DCBAA	Experimental	Drug: Pilocarpine, Drug: PlaceboSubjects 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

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (13 listed)

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:
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.

Key exclusion criteria (21 listed)

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.

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
PilocarpineAlso: Salagenoral	Drug	Treatment Sequence ABCDD, Treatment Sequence BDACC, Treatment Sequence CADBB, Treatment Sequence DCBAA
Placebooral	Drug	Treatment Sequence ABCDD, Treatment Sequence BDACC, Treatment Sequence CADBB, Treatment Sequence DCBAA

Primary outcome

Pharmacodynamic parameter salivary secretion at specified time points
Time frame: Days 1-5
Measure (mg/min) salivary secretion at specific timepoints
Pharmacodynamics assessed by area under the effect-time curve (AUE), saliva (AUEsal)
Time frame: Days 1-5
Pharmacodynamics assessed by maximal effect (Emax), saliva (Emax, sal)
Time frame: Days 1-5
Pharmacodynamics assessed by time at which the maximum salivary flow occurs (tmax, sal)
Time frame: Days 1-5

3 secondary outcomes

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
Safety profile assessed by adverse events, vital signs, routine electrocardiograms (ECG) , and clinical laboratory tests
Time frame: 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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.

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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.

Associate Medical Director study director

Astellas Pharma Europe B.V.

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 Pilocarpine in people with Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in United Kingdom.

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 13 inclusion and 21 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 13 Aug 2015. 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 Kingdom. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Pharmacodynamic parameter salivary secretion at specified time points (time frame: Days 1-5). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02447315.

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 13 Aug 2015.