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To assess the effect of immediate-release guanfacine hydrochloride, administered at therapeutic and supratherapeutic doses, on QT/QTc in healthy normal males and females
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Immediate-release Guanfacine HCl | Experimental |
| |
| Moxifloxacin HCl | Active Comparator |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| immediate release guanfacine hydrochloride | Drug | Subjects will receive 2x2mg immediate-release guanfacine on day 1. Subjects will receive 4x2mg immediate-release guanfacine on day 6. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Electrocardiogram Results (QTcNi) at Time of Maximum Plasma Concentration (Tmax) on Day 1 | QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline, Tmax (time of subject-specific maximum plasma concentration) |
| Change From Baseline in Electrocardiogram Results (QTcNi) at Tmax on Day 6 | QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
| Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 1 | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
| Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 6 | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 1 | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose | |
| Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 6 | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charles River Clinical Services Northwest, Inc. | Tacoma | Washington | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25109412 | Derived | Martin P, Satin L, Kahn RS, Robinson A, Corcoran M, Purkayastha J, Youcha S, Ermer JC. A thorough QT study of guanfacine. Int J Clin Pharmacol Ther. 2015 Apr;53(4):301-16. doi: 10.5414/CP202065. |
| Label | URL |
|---|---|
| FDA recall information | View source |
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This is a three period crossover trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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). |
| FG002 | 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). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention |
|
| |||||||||||||||||||||
| Second Intervention |
| ||||||||||||||||||||||
| Third Intervention |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Electrocardiogram Results (QTcNi) at Time of Maximum Plasma Concentration (Tmax) on Day 1 | QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Pharmacodynamic (PD) population consists of all evaluable subjects with no major protocol deviations. "Evaluable" subjects were defined as subjects who received a Day 6 dose and had Day 6 data for the primary and secondary endpoints for all three periods. | Posted | Least Squares Mean | Standard Error | msec | Baseline, Tmax (time of subject-specific maximum plasma concentration) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Guanfacine | Immediate-release Guanfacine HCl |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry mouth | Gastrointestinal disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| D016316 | Guanfacine |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D010648 | Phenylacetates |
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|
| moxifloxacin | Drug | Subjects will receive 400mg of moxifloxacin on day 1. Subjects will receive 400mg of moxifloxacin on day 6. |
|
|
| Placebo | Drug | Subjects will receive placebo on Day 1. Subjects will receive placebo on Day 6. |
|
| Change From Baseline in Heart Rate (HR) at Tmax on Day 1 | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
| Change From Baseline in Heart Rate (HR) at Tmax on Day 6 | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
| Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 1 | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
| Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 6 | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
| Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 1 | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
| Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 6 | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
| Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 1 | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
| Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 6 | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
| FDA-approved label | View source |
| Sponsor decision |
|
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
|
| BG001 | 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). |
| BG002 | 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). |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Moxifloxacin | 400 mg Avelox, positive control |
| OG002 | Placebo (Guanfacine) |
| OG003 | Placebo (Moxifloxacin) |
|
|
|
| Primary | Change From Baseline in Electrocardiogram Results (QTcNi) at Tmax on Day 6 | QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | PD population | Posted | Least Squares Mean | Standard Error | msec | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
|
|
|
|
| Primary | Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 1 | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | PD population | Posted | Least Squares Mean | Standard Error | msec | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
|
|
|
|
| Primary | Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 6 | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | PD population | Posted | Least Squares Mean | Standard Error | msec | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
|
|
|
|
| Primary | Change From Baseline in Heart Rate (HR) at Tmax on Day 1 | PD population | Posted | Least Squares Mean | Standard Error | bpm | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
|
|
|
|
| Primary | Change From Baseline in Heart Rate (HR) at Tmax on Day 6 | PD population | Posted | Least Squares Mean | Standard Error | bpm | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
|
|
|
|
| Primary | Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 1 | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). | PD population | Posted | Least Squares Mean | Standard Error | msec | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
|
|
|
|
| Primary | Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 6 | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). | PD population | Posted | Least Squares Mean | Standard Error | msec | Baseline and Tmax (time of subject-specific maximum plasma concentration) |
|
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 1 | Pharmacokinetic (PK) population consists of all subjects in the safety population (subjects who had taken one dose of study medication and had one follow-up safety assessment completed) who had evaluable concentration-time profiles. | Posted | Mean | Standard Deviation | ng/ml | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 6 | PK population | Posted | Mean | Standard Deviation | ng/ml | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
|
|
|
| Secondary | Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 1 | PK population | Posted | Mean | Standard Deviation | hours | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
|
|
|
| Secondary | Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 6 | PK population | Posted | Mean | Standard Deviation | hours | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
|
|
|
| Secondary | Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 1 | PK population | Posted | Mean | Standard Deviation | ng.h/ml | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
|
|
|
| Secondary | Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 6 | PK population | Posted | Mean | Standard Deviation | ng.h/ml | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose |
|
|
|
| 5 |
| 76 |
| 76 |
| 76 |
| EG001 | Moxifloxacin | Avelox, positive control | 0 | 72 | 46 | 72 |
| EG002 | Placebo | 0 | 68 | 39 | 68 |
| Ileus | Gastrointestinal disorders |
|
| Syncope | Nervous system disorders |
|
| Syncope vasovagal | Nervous system disorders |
|
| Orthostatic hypotension | Vascular disorders |
|
| Dizziness | Nervous system disorders |
|
| Asthenia | General disorders |
|
| Constipation | Gastrointestinal disorders |
|
| Headache | Nervous system disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Tinnitus | Ear and labyrinth disorders |
|
| Vision blurred | Eye disorders |
|
| Abdominal pain | Gastrointestinal disorders |
|
| Dry eye | Eye disorders |
|
| Mucosal dryness | General disorders |
|
| Eustachian tube dysfunction | Ear and labyrinth disorders |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders |
|
| Insomnia | Psychiatric disorders |
|
| Myalgia | Musculoskeletal and connective tissue disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Dyspepsia | Gastrointestinal disorders |
|
| Fatigue | General disorders |
|
| Hypoacusis | Ear and labyrinth disorders |
|
| Paresthesia | Nervous system disorders |
|
| Scotoma | Eye disorders |
|
| Abdominal distension | Gastrointestinal disorders |
|
| Anxiety | Psychiatric disorders |
|
| Hot flush | Vascular disorders |
|
| Hypotension | Vascular disorders |
|
| Irritability | General disorders |
|
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
| D000146 |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Mean Difference (Final Values) |
| 13.13 |
| 90 |
| 9.33 |
| 16.93 |
| Superiority or Other (legacy) |
| Mean Difference (Final Values) |
| 11.11 |
| 90 |
| 8.97 |
| 13.24 |
| Superiority or Other (legacy) |
| Mean Difference (Final Values) |
| 10.80 |
| 90 |
| 7.63 |
| 13.97 |
| Superiority or Other (legacy) |
| Mean Difference (Final Values) |
| 4.73 |
| 90 |
| 3.08 |
| 6.38 |
| Superiority or Other (legacy) |
| Mean Difference (Final Values) |
| 3.44 |
| 90 |
| 1.77 |
| 5.11 |
| Superiority or Other (legacy) |
| Mean Difference (Final Values) |
| 0.93 |
| 90 |
| -2.77 |
| 4.63 |
| Superiority or Other (legacy) |
| Mean Difference (Final Values) |
| 3.63 |
| 90 |
| -0.41 |
| 7.66 |
| Superiority or Other (legacy) |