A Drug Interaction Study of SPD503 and Concerta Administered Alone and In Combination in Normal Healthy Volunteers

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00901576
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 3
• Actual Duration (Months): 1.6
• Patients Per Site Per Month: 23.6

Study Details

Study Description

Brief Summary

This is a drug-drug interaction study; the purpose of this study is to examine the pharmacokinetics (levels of drug in the blood) of SPD503 (guanfacine hydrochloride) and Concerta (methylphenidate HCl) when given alone, and in combination.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: SPD503; Drug: Concerta; Drug: SPD503 + Concerta	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1, Open-label, Randomized, Three-period Crossover Drug Interaction Study Evaluating the Pharmacokinetic Profiles of SPD503 and CONCERTA, Administered Alone and in Combination in Healthy Adult Volunteers
• Actual Study Start Date: May 18, 2009
• Actual Primary Completion Date: Jul 6, 2009
• Actual Study Completion Date: Jul 6, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPD503	Drug: SPD503; SPD503 (guanfacine hydrochloride) extended-release 4 mg orally administered tablets; Other Names: Intuniv
Active Comparator: Concerta	Drug: Concerta; CONCERTA (methylphenidate HCl) extended-release 36 mg orally administered tablets.
Active Comparator: SPD503 + Concerta	Drug: SPD503 + Concerta; SPD503 4 mg + CONCERTA 36 mg orally administered tablets (taken together).

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) of Guanfacine [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

2. Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Guanfacine [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

3. Time of Maximum Plasma Concentration (Tmax) of Guanfacine [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

4. Time of Plasma Half-Life(T 1/2) of Guanfacine [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

5. Cmax of d-Methylphenidate [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

6. AUC of d-Methylphenidate [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

7. Tmax of d-Methylphenidate [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

8. T 1/2 of d-Methylphenidate [0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects must be normal healthy adult volunteers with no significant abnormalities in medical history, physical exam, vital signs or lab evaluations at the screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Biomedical Research, Inc.	Hackensack	New Jersey	United States	07601

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA recall information
• FDA-approved label

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00901576
• Other Study ID Numbers: SPD503-114
• First Posted: May 14, 2009
• Last Update Posted: Jun 14, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Shire: Healthy volunteers
• Additional relevant MeSH terms: Methylphenidate

Study Results

Participant Flow

Pre-assignment Detail	Study consists of 3 regimens: SPD503 (extended-release guanfacine HCl) single 4 mg dose, Concerta (extended-release methylphenidate HCl) single 36 mg dose, and SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered. Each dosing regimen is separated by a washout period and performed in 6 different dosing sequences.

Arm/Group Title	SPD503 First, Then Concerta, Then SPD503 + Concerta	SPD503 First, Then SPD503 + Concerta, Then Concerta	Concerta First, Then SPD503, Then SPD503 + Concerta	Concerta First, Then SPD503 + Concerta, Then SPD503	SPD503 + Concerta First, Then SPD503, Then Concerta	SPD503 + Concerta First, Then Concerta, Then SPD503
Arm/Group Description	SPD503 single 4 mg dose in first intervention, washout, Concerta single 36 mg dose in second intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in third intervention	SPD503 single 4 mg dose in first intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in second intervention, washout, Concerta single 36 mg dose in third intervention	Concerta single 36 mg dose in first intervention, washout, SPD503 single 4 mg dose in second intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in third intervention	Concerta single 36 mg dose in first intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in second intervention, washout, SPD503 single 4 mg dose in third intervention	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in first intervention, washout, SPD503 single 4 mg dose in second intervention, washout, Concerta single 36 mg dose in third intervention	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in first intervention, washout, Concerta single 36 mg dose in second intervention, washout, SPD503 single 4 mg dose in third intervention
Period Title: First Intervention
STARTED	6	7	7	6	6	6
COMPLETED	6	7	7	6	6	6
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	6	7	7	6	6	6
COMPLETED	6	7	7	6	6	6
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	6	7	7	6	6	6
COMPLETED	5	7	7	5	6	5
NOT COMPLETED	1	0	0	1	0	1
Period Title: First Intervention
STARTED	5	7	7	5	6	5
COMPLETED	5	7	7	5	6	5
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	5	7	7	5	6	5
COMPLETED	5	7	7	5	6	5
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	SPD503 First, Then Concerta, Then SPD503 + Concerta	SPD503 First, Then SPD503 + Concerta, Then Concerta	Concerta First, Then SPD503, Then SPD503 + Concerta	Concerta First, Then SPD503 + Concerta, Then SPD503	SPD503 + Concerta First, Then SPD503, Then Concerta	SPD503 + Concerta First, Then Concerta, Then SPD503	Total
Arm/Group Description	SPD503 single 4 mg dose in first intervention, washout, Concerta single 36 mg dose in second intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in third intervention	SPD503 single 4 mg dose in first intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in second intervention, washout, Concerta single 36 mg dose in third intervention	Concerta single 36 mg dose in first intervention, washout, SPD503 single 4 mg dose in second intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in third intervention	Concerta single 36 mg dose in first intervention, washout, SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in second intervention, washout, SPD503 single 4 mg dose in third intervention	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in first intervention, washout, SPD503 single 4 mg dose in second intervention, washout, Concerta single 36 mg dose in third intervention	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered in first intervention, washout, Concerta single 36 mg dose in second intervention, washout, SPD503 single 4 mg dose in third intervention	Total of all reporting groups
Overall Participants	6	7	7	6	6	6	38
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	7 100%	7 100%	6 100%	6 100%	6 100%	38 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.7 (5.54)	32.6 (6.70)	32.1 (8.01)	31.5 (8.41)	29.8 (2.64)	30.3 (5.68)	30.8 (6.28)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	1 14.3%	3 42.9%	1 16.7%	1 16.7%	2 33.3%	9 23.7%
Male	5 83.3%	6 85.7%	4 57.1%	5 83.3%	5 83.3%	4 66.7%	29 76.3%
Region of Enrollment (Count of Participants)
United States	6 100%	7 100%	7 100%	6 100%	6 100%	6 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of Guanfacine
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population (PKP) consists of all subjects in the Safety Population who had evaluable concentration-time profiles for guanfacine or d-methylphenidate. The Safety Population consists of all subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.

Arm/Group Title	SPD503 Alone	SPD503 + Concerta
Arm/Group Description	Single 4 mg dose of extended-release Guanfacine HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	37	36
Mean (Standard Deviation) [ng/ml]	2.6 (0.9)	2.7 (0.9)

2. Primary Outcome

Title	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Guanfacine
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PKP

Arm/Group Title	SPD503 Alone	SPD503 + Concerta
Arm/Group Description	Single 4 mg dose of extended-release Guanfacine HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	33	34
Mean (Standard Deviation) [ng*h/ml]	96.5 (37.3)	106.7 (39.9)

3. Primary Outcome

Title	Time of Maximum Plasma Concentration (Tmax) of Guanfacine
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PKP

Arm/Group Title	SPD503 Alone	SPD503 + Concerta
Arm/Group Description	Single 4 mg dose of extended-release Guanfacine HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	37	36
Mean (Standard Deviation) [hours]	8.1 (8.1)	8.7 (6.3)

4. Primary Outcome

Title	Time of Plasma Half-Life(T 1/2) of Guanfacine
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PKP

Arm/Group Title	SPD503 Alone	SPD503 + Concerta
Arm/Group Description	Single 4 mg dose of extended-release Guanfacine HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	33	34
Mean (Standard Deviation) [hours]	20.4 (7.9)	22.7 (10.6)

5. Primary Outcome

Title	Cmax of d-Methylphenidate
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PKP

Arm/Group Title	Concerta Alone	SPD503 + Concerta
Arm/Group Description	Single 36 mg dose of extended-release Methylphenidate HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	38	37
Mean (Standard Deviation) [ng/ml]	9.9 (2.8)	9.5 (2.9)

6. Primary Outcome

Title	AUC of d-Methylphenidate
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PKP

Arm/Group Title	Concerta Alone	SPD503 + Concerta
Arm/Group Description	Single 36 mg dose of extended-release Methylphenidate HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	32	32
Mean (Standard Deviation) [ng*h/ml]	102.8 (34.6)	100.5 (33.0)

7. Primary Outcome

Title	Tmax of d-Methylphenidate
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PKP

Arm/Group Title	Concerta Alone	SPD503 + Concerta
Arm/Group Description	Single 36 mg dose of extended-release Methylphenidate HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	38	37
Mean (Standard Deviation) [hours]	6.9 (1.0)	7.4 (1.3)

8. Primary Outcome

Title	T 1/2 of d-Methylphenidate
Time Frame	0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PKP

Arm/Group Title	Concerta Alone	SPD503 + Concerta
Arm/Group Description	Single 36 mg dose of extended-release Methylphenidate HCl	SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
Measure Participants	32	32
Mean (Standard Deviation) [hours]	3.9 (0.7)	4.1 (0.6)

Adverse Events

Adverse Event Reporting Description	Safety Population (SP) consisted of all subjects who received at least 1 dose of study drug and had at least 1 post-dose safety assessment
Arm/Group Title	SPD503 Alone		Concerta Alone		SPD503 + Concerta
Arm/Group Description	Single 4 mg dose of extended-release guanfacine HCl		Single 36 mg dose of extended-release methylphenidate HCl		SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
All Cause Mortality
	SPD503 Alone		Concerta Alone		SPD503 + Concerta
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SPD503 Alone		Concerta Alone		SPD503 + Concerta
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/37 (2.7%)		0/38 (0%)		0/37 (0%)
Nervous system disorders
Orthostatic syncope	1/37 (2.7%)		0/38 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	SPD503 Alone		Concerta Alone		SPD503 + Concerta
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/37 (16.2%)		8/38 (21.1%)		4/37 (10.8%)
Gastrointestinal disorders
Vomiting	0/37 (0%)		2/38 (5.3%)		0/37 (0%)
Nervous system disorders
Dizziness	1/37 (2.7%)		2/38 (5.3%)		1/37 (2.7%)
Dizziness postural	3/37 (8.1%)		0/38 (0%)		0/37 (0%)
Headache	2/37 (5.4%)		4/38 (10.5%)		3/37 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.