Efficacy of Cevimeline Versus Pilocarpine in the Secretion of Saliva

• Sponsor: University of Kentucky (Other)
• Overall Status: Completed
• CT.gov ID: NCT01690052
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 17.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The main objectives were: 1) To determine the efficacy of both cevimeline and pilocarpine in the secretion of saliva in patients with xerostomia, and 2) To compare the side-effects between the treatment for xerostomia with cevimeline and with pilocarpine.

Condition or Disease	Intervention/Treatment	Phase
Dry Mouth	Drug: Cevimeline; Drug: Pilocarpine	N/A

Detailed Description

Pilocarpine is a cholinergic agonist with predominant muscarinic action.As such, it acts at muscarinic-cholinergic receptors found throughout the body and promotes fluid secretion. Due to this, one of the main side-effects of pilocarpine is an increased amount of sweating. Thus, not only are the salivary glands stimulated, but all of the body's exocrine glands' production is heightened. On the other hand, cevimeline is a drug with a high affinity for specific muscarinic receptors (M3) located on lachrymal and salivary gland epithelium. At least in theory, cevimeline will produce less side effects compared with pilocarpine because of the higher affinity for the muscarinic receptors located in the salivary glands. A limited number of human clinical trials in the efficacy of cevimeline and pilocarpine to increase the production of saliva and the side effects have been performed with no conclusive results.

The main purposes of this study were to determine the efficacy of cevimeline and pilocarpine in the secretion of saliva in patients with xerostomia, and to compare the side-effects between these two medications.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Cevimeline vs. Pilocarpine in the Secretion of Saliva
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cevimeline Cevimeline vs Pilocarpine	Drug: Cevimeline; Cevimlenine Vs Pilocarpine, cross over design. Two sequences were evaluated "cevimeline first, then pilocarpine" and "pilocarpine first, then cevimeline". Each sequence was evaluated for 4 weeks with one week "washout" period in between both sequences. 15 patients were randomly assigned to a specific sequence by a research pharmacist independent from the study authors. The patients received 30mg of cevimeline three times a day and pilocarpine 5mg three times a day.
Active Comparator: Pilocarpine Pilocarpine vs. Cevimeline	Drug: Pilocarpine; Cevimlenine Vs Pilocarpine, cross over design, 4 weeks, one week wash out

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Saliva Production in ml. [4 weeks]

   The primary outcome measure was the change of stimulated and non-stimulated saliva in ml from the baseline record. At each appointment (weekly), participants will provide 2 saliva samples to measure their current salivary output. The first measurement will be obtained by having the patient spit as much as he or she could into a cup for five minutes. The amount of saliva in ml will be recorded. The second measurement will be obtained in a similar manner with the addition of having the patient chew on a block of unflavored wax. Patients will complete weekly questionnaires to help determine which side-effects they experience as they take the medications.

Other Outcome Measures

1. Adverse Events [four weeks]

   Adverse events related to the combination and order of study medication will be measured

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Potential candidates with the diagnosis of moderate-severe xerostomia were identified from the Oral Medicine Clinic at the University Of Kentucky College Of Dentistry, or self referrals in response to IRB approved study announcements. Enrollment required no clinical evidence of oral lesions, subjective perception of dry mouth and less than 2 mL of saliva collected in 5 minutes without stimulation. Exclusion criteria included patients with non controlled chronic obstructive pulmonary disease (COPD), depression, asthma, cardiac arrhythmias, glaucoma, and the current use of any medication with interactions with cevimeline and pilocarpine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kentucky Orofacial Pain Center College of Dentistry	Lexington	Kentucky	United States	40536

Sponsors and Collaborators

• University of Kentucky

Investigators

• Principal Investigator: Joel Thompson, PhD, University of Kentucky

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joel Thompson, PhD, PRS administrator, University of Kentucky
• ClinicalTrials.gov Identifier: NCT01690052
• Other Study ID Numbers: 9999
• First Posted: Sep 21, 2012
• Last Update Posted: Jun 4, 2018
• Last Verified: May 1, 2018

• Keywords provided by Joel Thompson, PhD, PRS administrator, University of Kentucky: dry mouth
• Additional relevant MeSH terms: Xerostomia; Pilocarpine; Cevimeline

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the Salivary Gland Dysfunction Clinic at the U. of K. A cross-over double-blind randomized trial was designed. Two arms were assembled. First arm the SEQUENCE was cevimeline(C) then pilocarpine(P), and for the second the SEQUENCE was P then C. Each participant received the drug for 4 weeks with 1 week washout period.
Pre-assignment Detail	The total number of patients screened for the study was 28. Of 28 patients, 15 met the inclusion criteria

Arm/Group Title	Cevimeline First, Then Pilocarpine	Pilocarpine First, Then Cevimeline
Arm/Group Description	Cevimeline First then Pilocarpine: Cevimeline (30mg three times a day) for 4 weeks (First intervention period) and then pilocarpine (5 mg three times a day) for 4 weeks (second intervention period). In between first and second intervention period, participants had a washout period for one week.	Pilocarpine First then Cevimeline: Pilocarpine (5 mg three times a day) for 4 weeks (first intervention period) and then Cevimeline (30mg three times a day) for 4 weeks (second intervention period). In between first and second intervention period, participants had a washout period for one week.
Period Title: FIRST INTERVENTION: 4 WEEKS
STARTED	7	8
COMPLETED	6	6
NOT COMPLETED	1	2
Period Title: FIRST INTERVENTION: 4 WEEKS
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0
Period Title: FIRST INTERVENTION: 4 WEEKS
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Two interventions were assembled: For the first intervention, the SEQUENCE was cevimeline (30mg three times a day) for 4 weeks and then Pilocarpine (5 mg three times a day) for 4 weeks, after the first sequence, the participants had a washout period for one week. For the second intervention, the SEQUENCE was Pilocarpine (5mg three times a day) or 4 weeks and then Cevimeline (30 mg three times a day) for 4 weeks, after the first sequence, the participants had a washout period for one week.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	3 20%
Male	12 80%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Saliva Production in ml.
Description	The primary outcome measure was the change of stimulated and non-stimulated saliva in ml from the baseline record. At each appointment (weekly), participants will provide 2 saliva samples to measure their current salivary output. The first measurement will be obtained by having the patient spit as much as he or she could into a cup for five minutes. The amount of saliva in ml will be recorded. The second measurement will be obtained in a similar manner with the addition of having the patient chew on a block of unflavored wax. Patients will complete weekly questionnaires to help determine which side-effects they experience as they take the medications.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cevimeline	Pilocarpine
Arm/Group Description	Cevimeline 30mg administered three times a day in first intervention period or second intervention period for 4 weeks.	Pilocarpine 5 mg administered three times a day in either first intervention period or second intervention period
Measure Participants	12	12
Unstimulated Saliva	1.41 (0.5)	3.93 (0.5)
Stimulated Saliva	5.31 (0.5)	10.34 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cevimeline, Pilocarpine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANOVA
	Comments	The p-value is calculated from the ANOVA

2. Other Pre-specified Outcome

Title	Adverse Events
Description	Adverse events related to the combination and order of study medication will be measured
Time Frame	four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	The adverse events are reported per intervention (4 weeks with each medication)
Adverse Event Reporting Description	No adverse events were presented in any of the intervention sequences
Arm/Group Title	Cevimeline Then Pilocarpine (Intervention 1)		Pilocarpine Then Cevimeline (Intervention 2)
Arm/Group Description	Cevimeline then pilocarpine One week washout period		Pilocarpine then cevimeline One week washout period
All Cause Mortality
	Cevimeline Then Pilocarpine (Intervention 1)		Pilocarpine Then Cevimeline (Intervention 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Cevimeline Then Pilocarpine (Intervention 1)		Pilocarpine Then Cevimeline (Intervention 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Cevimeline Then Pilocarpine (Intervention 1)		Pilocarpine Then Cevimeline (Intervention 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)

Limitations/Caveats

There are limitations that affected this study. This is a pilot study with a relative low number of patients.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.