Guanfacine Immediate-release Electrocardiogram Results (QTc) Study

This study has been completed.

Study NCT00672984 Information provided by Shire Pharmaceutical Development

First Received on May 2, 2008. Last Updated on December 22, 2009 History of Changes

Results First Received: September 23, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Pharmacodynamics Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
Condition:	Healthy
Interventions:	Drug: immediate release guanfacine hydrochloride Drug: moxifloxacin Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This is a three period crossover trial.

Reporting Groups

	Description
Guanfacine First	Single 4 mg dose of immediate-release Guanfacine HCl on Day 1, 4 mg of immediate-release Guanfacine HCl bid on Days 2 and 3, 6 mg of immediate-release Guanfacine HCl bid on Days 4 and 5, and a single 8 mg dose of immediate-release Guanfacine HCl on Day 6 in first intervention period; single 400 mg dose of Moxifloxacin on Day 1, placebo bid on Days 2, 3, 4, and 5, and single 400 mg dose of Moxifloxacin on Day 6 in second intervention period (after washout period); single dose of placebo on Day 1, placebo bid on Days 2, 3, 4, and 5, and single dose of placebo on Day 6 in third intervention period (after washout period).
Moxifloxacin First	Single 400 mg dose of Moxifloxacin on Day 1, placebo bid on Days 2, 3, 4, and 5, and single 400 mg dose of Moxifloxacin on Day 6 in first intervention period; single dose of placebo on Day 1, placebo bid on Days 2, 3, 4, and 5, and single dose of placebo on Day 6 in second intervention period (after washout period); single 4 mg dose of immediate-release Guanfacine HCl on Day 1, 4 mg of immediate-release Guanfacine HCl bid on Days 2 and 3, 6 mg of immediate-release Guanfacine HCl bid on Days 4 and 5, and a single 8 mg dose of immediate-release Guanfacine HCl on Day 6 in third intervention period (after washout period).
Placebo First	Single dose of placebo on Day 1, placebo bid on Days 2, 3, 4, and 5, and single dose of placebo on Day 6 in first intervention period; single 4 mg dose of immediate-release Guanfacine HCl on Day 1, 4 mg of immediate-release Guanfacine HCl bid on Days 2 and 3, 6 mg of immediate-release Guanfacine HCl bid on Days 4 and 5, and a single 8 mg dose of immediate-release Guanfacine HCl on Day 6 in second intervention period (after washout period); single 400 mg dose of Moxifloxacin on Day 1, placebo bid on Days 2, 3, 4, and 5, and single 400 mg dose of Moxifloxacin on Day 6 in third intervention period (after washout period).

Participant Flow for 3 periods

Period 1: First Intervention

	Guanfacine First	Moxifloxacin First	Placebo First
STARTED	31	25	27
COMPLETED	22	23	25
NOT COMPLETED	9	2	2
Adverse Event	5	0	0
Withdrawal by Subject	1	2	2
Sponsor decision	3	0	0

Period 2: Second Intervention

	Guanfacine First	Moxifloxacin First	Placebo First
STARTED	22	23	25
COMPLETED	22	17	24
NOT COMPLETED	0	6	1
Non-compliance with facility policies	0	2	0
Withdrawal by Subject	0	3	0
Protocol Violation	0	1	1

Period 3: Third Intervention

	Guanfacine First	Moxifloxacin First	Placebo First
STARTED	22	17	24
COMPLETED	21	17	23
NOT COMPLETED	1	0	1
Adverse Event	1	0	1

Baseline Characteristics

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Reporting Groups

	Description
Guanfacine First	Single 4 mg dose of immediate-release Guanfacine HCl on Day 1, 4 mg of immediate-release Guanfacine HCl bid on Days 2 and 3, 6 mg of immediate-release Guanfacine HCl bid on Days 4 and 5, and a single 8 mg dose of immediate-release Guanfacine HCl on Day 6 in first intervention period; single 400 mg dose of Moxifloxacin on Day 1, placebo bid on Days 2, 3, 4, and 5, and single 400 mg dose of Moxifloxacin on Day 6 in second intervention period (after washout period); single dose of placebo on Day 1, placebo bid on Days 2, 3, 4, and 5, and single dose of placebo on Day 6 in third intervention period (after washout period).
Moxifloxacin First	Single 400 mg dose of Moxifloxacin on Day 1, placebo bid on Days 2, 3, 4, and 5, and single 400 mg dose of Moxifloxacin on Day 6 in first intervention period; single dose of placebo on Day 1, placebo bid on Days 2, 3, 4, and 5, and single dose of placebo on Day 6 in second intervention period (after washout period); single 4 mg dose of immediate-release Guanfacine HCl on Day 1, 4 mg of immediate-release Guanfacine HCl bid on Days 2 and 3, 6 mg of immediate-release Guanfacine HCl bid on Days 4 and 5, and a single 8 mg dose of immediate-release Guanfacine HCl on Day 6 in third intervention period (after washout period).
Placebo First	Single dose of placebo on Day 1, placebo bid on Days 2, 3, 4, and 5, and single dose of placebo on Day 6 in first intervention period; single 4 mg dose of immediate-release Guanfacine HCl on Day 1, 4 mg of immediate-release Guanfacine HCl bid on Days 2 and 3, 6 mg of immediate-release Guanfacine HCl bid on Days 4 and 5, and a single 8 mg dose of immediate-release Guanfacine HCl on Day 6 in second intervention period (after washout period); single 400 mg dose of Moxifloxacin on Day 1, placebo bid on Days 2, 3, 4, and 5, and single 400 mg dose of Moxifloxacin on Day 6 in third intervention period (after washout period).

Baseline Measures

	Guanfacine First	Moxifloxacin First	Placebo First	Total
Number of Participants [units: participants]	31	25	27	83
Age [units: participants]
<=18 years	0	0	0	0
Between 18 and 65 years	31	25	27	83
>=65 years	0	0	0	0
Age [units: years] Mean ± Standard Deviation	27.7 ± 7.55	30.8 ± 10.02	30.2 ± 8.71	29.4 ± 8.61
Gender [units: participants]
Female	16	13	14	43
Male	15	12	13	40
Region of Enrollment [units: participants]
United States	31	25	27	83

Outcome Measures

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1. Primary:

Change From Baseline in Electrocardiogram Results (QTcNi) at Time of Maximum Plasma Concentration (Tmax) on Day 1 [ Time Frame: Baseline, Tmax (time of subject-specific maximum plasma concentration) ]

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2. Primary:

Change From Baseline in Electrocardiogram Results (QTcNi) at Tmax on Day 6 [ Time Frame: Baseline and Tmax (time of subject-specific maximum plasma concentration) ]

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3. Primary:

Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 1 [ Time Frame: Baseline and Tmax (time of subject-specific maximum plasma concentration) ]

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4. Primary:

Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 6 [ Time Frame: Baseline and Tmax (time of subject-specific maximum plasma concentration) ]

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5. Primary:

Change From Baseline in Heart Rate (HR) at Tmax on Day 1 [ Time Frame: Baseline and Tmax (time of subject-specific maximum plasma concentration) ]

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6. Primary:

Change From Baseline in Heart Rate (HR) at Tmax on Day 6 [ Time Frame: Baseline and Tmax (time of subject-specific maximum plasma concentration) ]

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7. Primary:

Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 1 [ Time Frame: Baseline and Tmax (time of subject-specific maximum plasma concentration) ]

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8. Primary:

Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 6 [ Time Frame: Baseline and Tmax (time of subject-specific maximum plasma concentration) ]

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9. Secondary:

Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 1 [ Time Frame: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose ]

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10. Secondary:

Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 6 [ Time Frame: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose ]

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11. Secondary:

Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 1 [ Time Frame: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose ]

Show Outcome Measure 11

12. Secondary:

Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 6 [ Time Frame: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose ]

Show Outcome Measure 12

13. Secondary:

Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 1 [ Time Frame: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose ]

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14. Secondary:

Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 6 [ Time Frame: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Gerald Tremblay, MD
Organization: Shire Pharmaceutical
e-mail: gtremblay@shire.com

No publications provided

Responsible Party:	Gerald Tremblay, M.D., Shire Pharmaceutical
ClinicalTrials.gov Identifier:	NCT00672984 History of Changes
Other Study ID Numbers:	SPD503-112
Study First Received:	May 2, 2008
Results First Received:	September 23, 2009
Last Updated:	December 22, 2009
Health Authority:	United States: Food and Drug Administration