Study Evaluating the Pharmacokinetics of Doxylamine Succinate in Children

• Sponsor: Procter and Gamble (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00796315
• Collaborator: Consumer Healthcare Products Association (Other)
• Enrollment: 41
• Locations: 6
• Arm: 1
• Duration (Months): 6
• Patients Per Site: 6.8
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The primary goal of this study is to characterize the pharmacokinetics of doxylamine succinate in children ages 2 to < 18 years. Once characterized, these pediatric pharmacokinetic data will be pooled with historical adult PK data from other studies to assess whether the existing Over-the-Counter (OTC)doses provide comparable systemic drug exposure as that associated with efficacy in adults.

Condition or Disease	Intervention/Treatment	Phase
Allergic Rhinitis; Upper Respiratory Infection	Drug: Doxylamine Succinate USP	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: A Single-dose, Open-label, Multi-center Study Evaluating the Pharmacokinetics of Doxylamine Succinate in Children Ages 2 to < 18 Years
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doxylamine Succinate (USP) Doxylamine Succinate United States Pharmacopeia (USP)	Drug: Doxylamine Succinate USP; One dose of liquid, dosing range 3.125mg/7.5mL - 12.5mg/30mL; Other Names: Doxylamine Succinate United States Pharmacopeia (USP)

Outcome Measures

Primary Outcome Measures

1. AUC of Doxylamine [72 Hours]

   Area under the time-concentration curve for Doxylamine from 0 to 72 hours post-dose plus an extrapolated area from 72 hours to infinity.

2. Cmax of Doxylamine [72 Hours]

   Maximum concentration of Doxylamine from 0 to 72 hours post-dose

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• are male or female children ages 2 to < 18 years, with a minimum weight of 24 lbs and

5th percentile and < 95th percentile for weight based on age and sex, at the time of dosing study medication

• had a previous diagnosis of allergic rhinitis, or had a history of frequent upper respiratory infections (URI)/common cold and either be symptomatic, or at risk for future URI, including each of the following 3 criteria

• Frequency Criterion: > 6 infections per year for children aged 2 to <6 years of age and > 4 infections per year for children aged 6 to < 18 years of age

• Crowding Criterion: 4 persons living in the home or 3 persons sleeping in one bedroom

• Exposure Criterion: another family member in the home who is ill with URI / common cold or a child in the family who is attending preschool or school with 6 children in the group.

• are in good general health

• are likely to be compliant and complete the study and have parent(s) or legally authorized representative(s) likely to be compliant and complete the study according to the Investigator

• whose parent(s) or legally authorized representative(s) have signed and dated an Institutional Review Board (IRB)-approved consent form for the subject to participate in the study

• must have signed an assent form as required by the site's IRB

• if post-menarchal females, subjects must have a negative urine pregnancy test at screening and check-in, or serum pregnancy test at screening, if site required;

• if post-menarchal females, subjects must practice abstinence or use an effective form of birth control (eg, intrauterine device, low dose oral contraceptives [ 50g ethinyl estradiol], contraceptive implants or injections, diaphragm with spermicide, cervical cap, or consort use of condom) for at least 3 months before being enrolled in the study.

Exclusion Criteria:

• has any history or presence of the following medical conditions: peptic ulcer, pyloroduodenal obstruction or other gastrointestinal disease; renal or hepatic disease; diabetes mellitus; hyperthyroidism; cardiovascular disease;increased ocular pressure or glaucoma; endocrine, metabolic, hematologic or neoplastic disease; seizure disorder; chronic respiratory diseases including asthma, emphysema and chronic bronchitis; autoimmune disease; immunodeficiency tuberculosis; bladder neck obstruction; significant dermatologic condition.

• has a known sensitivity or allergy to doxylamine succinate

• has a history of a severe allergic reaction to any drug or has multiple food/drug allergies

• experienced febrile illness greater than 100°F within 7 days prior to dosing

• reports any known enzyme-inducer, enzyme-inhibitor, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides within 30 days prior to dosing, unless approved by the Sponsor

• reports any other prescription drug or herbal remedy usage within 14 days prior to dosing except for low dose contraceptives, unless approved by the Sponsor

• reports any non-prescription drug or supplemental vitamin usage within 5 days prior to dosing

• unwillingness to refrain from caffeine or other xanthine-containing beverages, including coffee and tea, alcohol, grapefruit juice, chocolate, or Seville oranges 24 hours prior to admission and throughout the study

• reported use of tobacco, smoking cessation products, or products containing nicotine within 3 months prior to Screening

• has an acute illness (except as described in Section 3.3.1 Inclusion Criterion b) within 14 days prior to dosing; unless approved by the Sponsor;

• has any laboratory value outside the laboratory reference range considered clinically significant by the Investigator

• has a history or diagnosis of Hepatitis B, Hepatitis C, human immunodeficiency virus (HIV), or thyroid disease

• has a history of alcohol or illicit drug use or a positive urine drug of abuse screen

• are pregnant or lactating (post-menarchal female subjects should be made aware that pregnancy testing will occur during the study, and that if they are sexually active they must take appropriate steps to ensure they do not become pregnant during the study)

• has made a blood donation or plasma donation within 4 weeks prior to dosing;

• has participated in another investigational drug study protocol within 30 days prior to dosing (Day -1)

• has a history or presence, upon clinical evaluation, of any illness or condition that might impact safety of the subject with test product administration or evaluability of drug effect, based on the Investigator's discretion

• is unable to avoid driving, operating machinery, or other tasks that require alertness during the study.

• is unable or unwilling to avoid contact sports, strenuous exercises (e.g. weight lifting), exercises for which they are not trained or conditioned or intramuscular injection for at least 1 week before baseline visit when creatine phosphokinase (CPK) will be evaluated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Best, MD	Washington	District of Columbia	United States	20010
2	Janice E. Sullivan, MD	Louisville	Kentucky	United States	40202
3	Margaret Ann Springer, MD	Shreveport	Louisiana	United States	71103
4	Bridgette Jones, MD	Kansas City	Missouri	United States	64108
5	Alex Kemper, Pharm D	Durham	North Carolina	United States	27705
6	Jeffrey L Blumer, MD, PhD	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• Procter and Gamble
• Consumer Healthcare Products Association

Investigators

• Study Director: Molly Seeck, BS, JD, Procter and Gamble

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Procter and Gamble
• ClinicalTrials.gov Identifier: NCT00796315
• Other Study ID Numbers: 2008014
• First Posted: Nov 24, 2008
• Last Update Posted: Feb 4, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Procter and Gamble: Pharmacokinetic study
• Additional relevant MeSH terms: Rhinitis; Respiratory Tract Infections; Rhinitis, Allergic; Doxylamine; Doxylamine succinate

Study Results

Participant Flow

Pre-assignment Detail	Participant flow is described by three different age groups based on dosing differences for each group

Arm/Group Title	Subjects Aged 2-5 Years (Doxylamine Succinate)	Aged 6-11 Years (Doxylamine Succinate	Subjects Aged 12-17 Years (Doxylamine Suc
Arm/Group Description	Ages 2-5 years. Doxylamine Succinate USP : One dose of liquid, dosing range 3.125mg/7.5mL - 12.5mg/30mL.	Ages 6-11 years. Doxylamine Succinate USP : One dose of liquid, dosing range 3.125mg/7.5mL - 12.5mg/30mL. Note: One subject (age group 6-11) was unable to meet protocol criteria (spit out a portion of his dosage) and was discontinued.	Ages 12-17 years. Doxylamine Succinate USP : One dose of liquid, dosing range 3.125mg/7.5mL - 12.5mg/30mL.
Period Title: Overall Study
STARTED	9	17	15
COMPLETED	9	16	15
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	Doxylamine Succinate USP
Arm/Group Description	Doxylamine Succinate, United States Pharmacopeia (USP): One dose of liquid, dosing range 3.125mg/7.5mL - 12.5mg/30mL.
Overall Participants	41
Age (Count of Participants)
<=18 years	41 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Subjects Aged 2-5 years	3.6 (1.1)
Subjects Aged 6-11 years	8.5 (1.5)
Subjects Aged 12-17 years	14.5 (1.8)
Sex/Gender, Customized (participants) [Number]
Male, Ages 2-5	7 17.1%
Female, Ages 2-5	2 4.9%
Male, Ages 6-11	9 22%
Female, Ages 6-11	8 19.5%
Male, Ages 12-17	9 22%
Female, Ages 12-17	6 14.6%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	AUC of Doxylamine
Description	Area under the time-concentration curve for Doxylamine from 0 to 72 hours post-dose plus an extrapolated area from 72 hours to infinity.
Time Frame	72 Hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects Aged 2-5 Years	Subjects Aged 6-11 Years	Subjects Aged 12-17 Years
Arm/Group Description	Ages 2-5 years. Subjects received a dose of either 3.125 or 4.17 mg Doxylamine Succinate USP (exact dose dependent upon body weight)	Ages 6-11 years. Subjects received a dose of 4.17 or 6.25 or 8.33 or 10.42 mg Doxylamine Succinate USP (exact dose dependent upon body weight). Note: One subject (age group 6-11) was unable to meet protocol criteria (spit out a portion of his dosage) and was discontinued.	Ages 12-17 years. All subjects received a dose of 12.5 mg Doxylamine Succinate USP
Measure Participants	9	16	15
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	461.9 (51.2)	810.1 (27.9)	827.0 (45.4)

2. Primary Outcome

Title	Cmax of Doxylamine
Description	Maximum concentration of Doxylamine from 0 to 72 hours post-dose
Time Frame	72 Hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subjects Aged 2-5 Years	Subjects Aged 6-11 Years	Subjects Aged 12-17 Years
Arm/Group Description	Ages 2-5 years. Doxylamine Succinate USP	Ages 6-11 years. Doxylamine Succinate USP	Ages 12-17 years. Doxylamine Succinate USP
Measure Participants	9	16	15
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	50.1 (22.5)	65.8 (19.9)	63.2 (42.9)

Adverse Events

Time Frame	Adverse Events collected until discharge from study, approximately 72 hours after dose
Arm/Group Title	Subjects Aged 2-5 Years		Aged 6-11 Years		Subjects Aged 12-17 Years
Arm/Group Description	Ages 2-5 years. Doxylamine Succinate USP		Ages 6-11 years. Doxylamine Succinate USP		Ages 12-17 years. Doxylamine succinate USP
All Cause Mortality
	Subjects Aged 2-5 Years		Aged 6-11 Years		Subjects Aged 12-17 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Subjects Aged 2-5 Years		Aged 6-11 Years		Subjects Aged 12-17 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/17 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Subjects Aged 2-5 Years		Aged 6-11 Years		Subjects Aged 12-17 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)		4/17 (23.5%)		7/15 (46.7%)
Infections and infestations
Otitis media acute	0/9 (0%)	0	1/17 (5.9%)	1	0/15 (0%)	0
Nervous system disorders
Sedation	4/9 (44.4%)	5	3/17 (17.6%)	3	5/15 (33.3%)	5
Somnolence	1/9 (11.1%)	1	0/17 (0%)	0	2/15 (13.3%)	2
Headache	0/9 (0%)	0	0/17 (0%)	0	1/15 (6.7%)	1
Dizziness	0/9 (0%)	0	0/17 (0%)	0	1/15 (6.7%)	1

Limitations/Caveats

Incidences of mild sedation are consistent with doxylamine's indication as an OTC sleep aid. Conclusive evaluation of sedation couldn't be undertaken in the absence of a control group. Also, children may nap in daytime confounding sedation assessment

More Information

Certain Agreements

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

The Investigator and Sub-Investigators agree that all data, calculations, interpretations, opinions, and recommendations regarding the study will be the property of the Sponsor. The Investigator agrees to consider the results as information subject to confidentiality and use restrictions.