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

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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00901576
Enrollment
38
Registered
2009-05-14
Start date
2009-05-18
Completion date
2009-07-06
Last updated
2021-06-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Healthy volunteers

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.

Interventions

DRUGSPD503

SPD503 (guanfacine hydrochloride) extended-release 4 mg orally administered tablets

DRUGConcerta

CONCERTA (methylphenidate HCl) extended-release 36 mg orally administered tablets.

DRUGSPD503 + Concerta

SPD503 4 mg + CONCERTA 36 mg orally administered tablets (taken together).

Sponsors

Shire
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 45 Years
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

Design outcomes

Primary

MeasureTime frame
Maximum Plasma Concentration (Cmax) of Guanfacine0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Guanfacine0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
Time of Maximum Plasma Concentration (Tmax) of Guanfacine0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
Time of Plasma Half-Life(T 1/2) of Guanfacine0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
Cmax of d-Methylphenidate0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
AUC of d-Methylphenidate0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
Tmax of d-Methylphenidate0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
T 1/2 of d-Methylphenidate0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose

Countries

United States

Participant flow

Pre-assignment details

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.

Participants by arm

ArmCount
SPD503 First, Then Concerta, Then SPD503 + Concerta
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
6
SPD503 First, Then SPD503 + Concerta, Then Concerta
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
7
Concerta First, Then SPD503, Then SPD503 + Concerta
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
7
Concerta First, Then SPD503 + Concerta, Then SPD503
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
6
SPD503 + Concerta First, Then SPD503, Then Concerta
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
6
SPD503 + Concerta First, Then Concerta, Then SPD503
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
6
Total38

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Second InterventionPhysician Decision100000
Second InterventionWithdrawal by Subject000101

Baseline characteristics

CharacteristicSPD503 First, Then SPD503 + Concerta, Then ConcertaConcerta First, Then SPD503, Then SPD503 + ConcertaConcerta First, Then SPD503 + Concerta, Then SPD503SPD503 First, Then Concerta, Then SPD503 + ConcertaSPD503 + Concerta First, Then SPD503, Then ConcertaSPD503 + Concerta First, Then Concerta, Then SPD503Total
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
7 Participants7 Participants6 Participants6 Participants6 Participants6 Participants38 Participants
Age, Continuous32.6 years
STANDARD_DEVIATION 6.7
32.1 years
STANDARD_DEVIATION 8.01
31.5 years
STANDARD_DEVIATION 8.41
27.7 years
STANDARD_DEVIATION 5.54
29.8 years
STANDARD_DEVIATION 2.64
30.3 years
STANDARD_DEVIATION 5.68
30.8 years
STANDARD_DEVIATION 6.28
Region of Enrollment
United States
7 Participants7 Participants6 Participants6 Participants6 Participants6 Participants38 Participants
Sex: Female, Male
Female
1 Participants3 Participants1 Participants1 Participants1 Participants2 Participants9 Participants
Sex: Female, Male
Male
6 Participants4 Participants5 Participants5 Participants5 Participants4 Participants29 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
6 / 378 / 384 / 37
serious
Total, serious adverse events
1 / 370 / 380 / 37

Outcome results

Primary

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

Population: PKP

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneArea Under the Steady-state Plasma Concentration-time Curve (AUC) of Guanfacine96.5 ng*h/mlStandard Deviation 37.3
SPD503 + ConcertaArea Under the Steady-state Plasma Concentration-time Curve (AUC) of Guanfacine106.7 ng*h/mlStandard Deviation 39.9
Primary

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

Population: PKP

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneAUC of d-Methylphenidate102.8 ng*h/mlStandard Deviation 34.6
SPD503 + ConcertaAUC of d-Methylphenidate100.5 ng*h/mlStandard Deviation 33
Primary

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

Population: PKP

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneCmax of d-Methylphenidate9.9 ng/mlStandard Deviation 2.8
SPD503 + ConcertaCmax of d-Methylphenidate9.5 ng/mlStandard Deviation 2.9
Primary

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

Population: 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.

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneMaximum Plasma Concentration (Cmax) of Guanfacine2.6 ng/mlStandard Deviation 0.9
SPD503 + ConcertaMaximum Plasma Concentration (Cmax) of Guanfacine2.7 ng/mlStandard Deviation 0.9
Primary

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

Population: PKP

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneT 1/2 of d-Methylphenidate3.9 hoursStandard Deviation 0.7
SPD503 + ConcertaT 1/2 of d-Methylphenidate4.1 hoursStandard Deviation 0.6
Primary

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

Population: PKP

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneTime of Maximum Plasma Concentration (Tmax) of Guanfacine8.1 hoursStandard Deviation 8.1
SPD503 + ConcertaTime of Maximum Plasma Concentration (Tmax) of Guanfacine8.7 hoursStandard Deviation 6.3
Primary

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

Population: PKP

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneTime of Plasma Half-Life(T 1/2) of Guanfacine20.4 hoursStandard Deviation 7.9
SPD503 + ConcertaTime of Plasma Half-Life(T 1/2) of Guanfacine22.7 hoursStandard Deviation 10.6
Primary

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

Population: PKP

ArmMeasureValue (MEAN)Dispersion
SPD503 AloneTmax of d-Methylphenidate6.9 hoursStandard Deviation 1
SPD503 + ConcertaTmax of d-Methylphenidate7.4 hoursStandard Deviation 1.3

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026