Trial Outcomes & Findings for A Drug Interaction Study of SPD503 and Concerta Administered Alone and In Combination in Normal Healthy Volunteers (NCT NCT00901576)
NCT ID: NCT00901576
Last Updated: 2021-06-14
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
38 participants
Primary outcome timeframe
0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dose
Results posted on
2021-06-14
Participant Flow
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.
Participant milestones
| Measure |
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
|
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
|
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
|
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
|
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
|
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
|
|---|---|---|---|---|---|---|
|
First Intervention
STARTED
|
6
|
7
|
7
|
6
|
6
|
6
|
|
First Intervention
COMPLETED
|
6
|
7
|
7
|
6
|
6
|
6
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout
STARTED
|
5
|
7
|
7
|
5
|
6
|
5
|
|
Washout
COMPLETED
|
5
|
7
|
7
|
5
|
6
|
5
|
|
Washout
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Second Intervention
STARTED
|
6
|
7
|
7
|
6
|
6
|
6
|
|
Second Intervention
COMPLETED
|
5
|
7
|
7
|
5
|
6
|
5
|
|
Second Intervention
NOT COMPLETED
|
1
|
0
|
0
|
1
|
0
|
1
|
|
Third Intervention
STARTED
|
5
|
7
|
7
|
5
|
6
|
5
|
|
Third Intervention
COMPLETED
|
5
|
7
|
7
|
5
|
6
|
5
|
|
Third Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
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
|
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
|
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
|
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
|
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
|
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
|
|---|---|---|---|---|---|---|
|
Second Intervention
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
1
|
|
Second Intervention
Physician Decision
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Drug Interaction Study of SPD503 and Concerta Administered Alone and In Combination in Normal Healthy Volunteers
Baseline characteristics by cohort
| Measure |
SPD503 First, Then Concerta, Then SPD503 + Concerta
n=6 Participants
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 First, Then SPD503 + Concerta, Then Concerta
n=7 Participants
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 First, Then SPD503, Then SPD503 + Concerta
n=7 Participants
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 First, Then SPD503 + Concerta, Then SPD503
n=6 Participants
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 + Concerta First, Then SPD503, Then Concerta
n=6 Participants
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 + Concerta First, Then Concerta, Then SPD503
n=6 Participants
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
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
38 Participants
n=115 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Continuous
|
27.7 years
STANDARD_DEVIATION 5.54 • n=5 Participants
|
32.6 years
STANDARD_DEVIATION 6.70 • n=7 Participants
|
32.1 years
STANDARD_DEVIATION 8.01 • n=5 Participants
|
31.5 years
STANDARD_DEVIATION 8.41 • n=4 Participants
|
29.8 years
STANDARD_DEVIATION 2.64 • n=21 Participants
|
30.3 years
STANDARD_DEVIATION 5.68 • n=10 Participants
|
30.8 years
STANDARD_DEVIATION 6.28 • n=115 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
29 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
38 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: 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.
Outcome measures
| Measure |
SPD503 Alone
n=37 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=36 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Guanfacine
|
2.6 ng/ml
Standard Deviation 0.9
|
2.7 ng/ml
Standard Deviation 0.9
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: PKP
Outcome measures
| Measure |
SPD503 Alone
n=33 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=34 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Guanfacine
|
96.5 ng*h/ml
Standard Deviation 37.3
|
106.7 ng*h/ml
Standard Deviation 39.9
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: PKP
Outcome measures
| Measure |
SPD503 Alone
n=37 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=36 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Guanfacine
|
8.1 hours
Standard Deviation 8.1
|
8.7 hours
Standard Deviation 6.3
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: PKP
Outcome measures
| Measure |
SPD503 Alone
n=33 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=34 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
Time of Plasma Half-Life(T 1/2) of Guanfacine
|
20.4 hours
Standard Deviation 7.9
|
22.7 hours
Standard Deviation 10.6
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: PKP
Outcome measures
| Measure |
SPD503 Alone
n=38 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=37 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
Cmax of d-Methylphenidate
|
9.9 ng/ml
Standard Deviation 2.8
|
9.5 ng/ml
Standard Deviation 2.9
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: PKP
Outcome measures
| Measure |
SPD503 Alone
n=32 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=32 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
AUC of d-Methylphenidate
|
102.8 ng*h/ml
Standard Deviation 34.6
|
100.5 ng*h/ml
Standard Deviation 33.0
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: PKP
Outcome measures
| Measure |
SPD503 Alone
n=38 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=37 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
Tmax of d-Methylphenidate
|
6.9 hours
Standard Deviation 1.0
|
7.4 hours
Standard Deviation 1.3
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30, 48 and 72 hours post-dosePopulation: PKP
Outcome measures
| Measure |
SPD503 Alone
n=32 Participants
Single 4 mg dose of extended-release Guanfacine HCl
|
SPD503 + Concerta
n=32 Participants
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|
|
T 1/2 of d-Methylphenidate
|
3.9 hours
Standard Deviation 0.7
|
4.1 hours
Standard Deviation 0.6
|
Adverse Events
SPD503 Alone
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Concerta Alone
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
SPD503 + Concerta
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SPD503 Alone
n=37 participants at risk
Single 4 mg dose of extended-release guanfacine HCl
|
Concerta Alone
n=38 participants at risk
Single 36 mg dose of extended-release methylphenidate HCl
|
SPD503 + Concerta
n=37 participants at risk
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|---|
|
Nervous system disorders
Orthostatic syncope
|
2.7%
1/37
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
|
0.00%
0/38
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
|
0.00%
0/37
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
|
Other adverse events
| Measure |
SPD503 Alone
n=37 participants at risk
Single 4 mg dose of extended-release guanfacine HCl
|
Concerta Alone
n=38 participants at risk
Single 36 mg dose of extended-release methylphenidate HCl
|
SPD503 + Concerta
n=37 participants at risk
SPD503 (single 4 mg dose) + Concerta (single 36 mg dose) coadministered
|
|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/37
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
|
5.3%
2/38
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
|
0.00%
0/37
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
|
|
Nervous system disorders
Dizziness
|
2.7%
1/37
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
|
5.3%
2/38
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
|
2.7%
1/37
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
|
|
Nervous system disorders
Dizziness postural
|
8.1%
3/37
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
|
0.00%
0/38
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
|
0.00%
0/37
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
|
|
Nervous system disorders
Headache
|
5.4%
2/37
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
|
10.5%
4/38
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
|
8.1%
3/37
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
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER