A Study to Evaluate the Efficacy and Safety of Two Doses of PF-03654746 in Adults With Attention Deficit Hyperactivity Disorder (ADHD).

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

A Phase Iia, Randomized, Double Blind, Placebo Controlled, Three-treatment, Two-period Crossover Study Of The Efficacy And Safety Of Two Doses Of Pf-03654746 In Adults With Attention Deficit Hyperactivity Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00531752
• Other study ID #: A8801004
• Secondary ID: 3-WK, CO MTD IN
• Status: Completed
• Phase: Phase 2
• First received: September 18, 2007
• Last updated: January 22, 2016
• Start date: December 2007
• Est. completion date: September 2008

Study information

• Verified date: January 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether PF-03654746 is effective in the treatment of Adult Attention Deficit Hyperactivity Disorder (ADHD). This will be a randomized, double-blind, crossover study in which adults with ADHD will receive 3 weeks of treatment with PF-03654746, either a low dose (1 mg), or flexible dose (0.50 mg titrated up to 2 mg), and 3 weeks of placebo. A washout period will separate the 2 treatment periods. Participants will be required to washout of prior ADHD medication before entering the study. Participants will be required to come to the site for 10 visits over approximately a 10-week period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

Subjects with a diagnosis of Attention Deficit Hyperactivity Disorder, based on clinical assessment and interview.

Male and female outpatients. Subjects with a diagnosis of Attention Deficit Hyperactivity Disorder, based on clinical assessment and interview.

Female subjects must be of non-childbearing potential.

Exclusion Criteria:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including hypertension), hepatic, neurologic, or allergic disease.

Current or lifetime history of psychosis or bipolar disorder; any current anxiety disorder (with the exception of social or specific phobia), or substance abuse or dependence in the past 6 months.

Current episode of Major Depression or episode within the last 6 months.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• PF-03654746
Dosage Form: 0.5 mg capsules of PF-03654746 Dosage: 0.5 mg QD for Days 1-7, then 1.0 mg QD Days 8-14, then 2.0 mg QD Days 15-21
• Placebo capsules
Dosage Form: matching placebo capsules Dosage: Subjects will take two placebo capsules each morning throughout the 3 week double-blind treatment placebo treatment period.
• PF-03654746
Dosage Form: 0.5 mg capsules of PF-03654746 Dosage: 1 mg (2 x 0.5 mg capsules) of PF-03654746 given daily for three weeks

Locations

Country	Name	City	State
United States	Massachusetts General Hospital, ADHD Program	Cambridge	Massachusetts
United States	The University of Illinois at Chicago, Institute for Juvenile Research	Chicago	Illinois
United States	NeuroScience, Inc	Herndon	Virginia
United States	Bay Area Research Institute	Lafayette	California
United States	Pharmacology Research Institute	Los Alamitos	California
United States	New York University School of Medicine	New York	New York
United States	Pharmacology Research Institute	Newport Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Medical Outcome Study - Sleep Scale (MOS-SS) Subscale Scores at Week 1, 2 and 3	Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep, and overall sleep problem index (SPI) I (range 0 to 600) and II. Except for sleep quantity and sleep problem index I, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.	Baseline, Week 1, 2, 3	Yes
Other	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Latency Subscale Scores at Week 1, 2 and 3	SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total awake after sleep onset (WASO [1 item]), quality of sleep (1 item). Latency subscale score ranges from 0-840 minutes. Lower value indicates better sleep.	Baseline, Week 1, 2, 3	No
Other	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Hours of Sleep Subscale Scores at Week 1, 2 and 3	SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item).; Hours of sleep subscale score ranges from 0-16 hours. Higher value indicates better sleep.	Baseline, Week 1, 2, 3	No
Other	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Number of Awakenings Subscale Scores at Week 1, 2 and 3	SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item).; Number of awakenings subscale score ranges from 0 to 30. Lower value indicates better sleep.	Baseline, Week 1, 2, 3	No
Other	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Total Awake After Sleep Onset (WASO) Subscale Scores at Week 1, 2 and 3	SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item).; Total WASO subscale score ranges from 0 to 24 hours. Lower value indicates better sleep.	Baseline, Week 1, 2, 3	No
Other	Change From Baseline in Subjective Sleep Questionnaire (SSQ) Quality of Sleep Subscale Scores at Week 1, 2 and 3	SSQ is a 5-item self-report scale that was designed to evaluate the amount and quality of sleep and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), WASO (1 item), quality of sleep (1 item).; Quality of sleep subscale score ranges from 0-100. Higher score indicates better quality of sleep.	Baseline, Week 1, 2, 3	No
Other	Number of Participants With Clinically Significant Laboratory Test Abnormalities	Laboratory parameters included hematology (hemoglobin, hematocrit, red blood cell count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); liver function (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein); renal function (creatinine, blood urea nitrogen, uric acid, sodium, potassium, chloride, bicarbonate, calcium); urinalysis (protein, blood), and clinical chemistry (glucose).	Baseline up to 1 week after last study dose	Yes
Other	Number of Participants With Electrocardiogram (ECG) Findings	Criteria for potential clinical concern in ECG parameters: maximum PR interval of greater than or equal to (>=) 300 milliseconds (msec), maximum QRS interval >=200 msec, maximum QTc interval of 450 to <480 msec, 480 to <500 msec and >=500 msec.	Baseline up to End of Treatment (Week 3 of period 2)	Yes
Other	Number of Participants With Clinically Significant Vital Sign Abnormalities	Criteria for potential clinical concern in vital signs: systolic blood pressure (BP) less than (<) 90 millimeters of mercury (mmHg), diastolic BP <50 mmHg, supine and sitting heart rate <40 beats per minute (bpm) or >120 bpm, standing and erect heart rate <40 bpm or >140 bpm. Maximum increase from baseline in systolic BP >=30 mmHg, maximum increase from baseline in diastolic BP >=20 mmHg.	Baseline up to 1 week after last study dose	Yes
Other	Number of Participants With Change From Baseline in Physical Examination and Neurological Examination	Analysis include general physical examination and assessment of head, ears, eyes, ocular fundi, nose, mouth, throat, neck, thyroid, lungs, heart, breasts, abdomen and musculoskeletal system.	Baseline up to 1 week after last study dose (1 week after end of Period 2)	Yes
Other	Treatment Duration	Treatment duration was defined as the total number of dosing days from first to last day of study drug administration in each period.	Day 1 up to Day 21	No
Primary	Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 3	AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.	Baseline, Week 3	No
Secondary	Change From Baseline in Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Total Score at Week 1 and 2	AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.	Baseline, Week 1, 2	No
Secondary	Percentage of Participants With at Least 30 Percent Decrease From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score	AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.	Week 1, 2, 3	No
Secondary	Percentage of Participants With 1 or 2 Score on Clinical Global Impression-Severity Scale (CGI-S)	CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Participants with a score of 1 (normal - not ill at all) or 2 (borderline mentally ill) are reported.	Week 1, 2, 3	No
Secondary	Percentage of Participants With Less Than or Equal to 18 Score on Adult ADHD Investigator Symptom Rating Scale (AISRS)	AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.	Week 1, 2, 3	No
Secondary	Percentage of Participants With Sustained Response of at Least 30 Percent Decrease From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score	TASS: a time sensitive 18-item questionnaire completed by the participant that measured the severity of current ADHD symptoms. It included 9 items that evaluate symptoms of inattention sub-scale and 9 items that evaluate symptoms of impulsivity and hyperactivity sub-scale. Each item was rated from 0 (none) to 3 (severe). TASS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher total score corresponds to a worse severity of ADHD. TASS was administered each day from Day 1 to 14 and on Day 21 in each intervention period. Participants with sustained response were those who had at least 30 percent decrease from baseline in TASS total score, which was maintained at all visits up to the time of assessment. Sustained responders at Day 7, 14 and 21 were analyzed.	Day 7, 14, 21	No
Secondary	Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) Subscale Scores at Week 1, 2 and 3	AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). The AISRS inattention and hyperactive/impulsive total subscale score range from 0 to 27. A higher total subscale score corresponded to a worse severity of ADHD inattention or hyperactivity/impulsivity.	Baseline, Week 1, 2, 3	No
Secondary	Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Total Score on Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 21	TASS: a time sensitive 18-item questionnaire completed by the participant that measured the severity of current ADHD symptoms. It included 9 items that evaluate symptoms of inattention sub-scale and 9 items that evaluate symptoms of impulsivity and hyperactivity sub-scale. Each item was rated from 0 (none) to 3 (severe). TASS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher total score corresponded to a worse severity of ADHD. TASS was administered each day from Day 1 to 14 and on Day 21 in each intervention period.	Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21	No
Secondary	Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Week 3	The MADRS scale measures the depression level of a participant. It is administered as a semi-structured clinician interview. The total score is derived by adding the scores of the following 10 items: (1) Apparent sadness; (2) Reported sadness; (3) Inner tension; (4) Reduced sleep; (5) Reduced appetite; (6) Concentration difficulties; (7) Lassitude; (8) Inability to feel; (9) Pessimistic thoughts; (10) Suicidal thoughts. Each item is scored using a 6-point scale which ranges from 0 to 6 (a higher score indicates increased severity). The total score range was 0 to 60 where 0 indicates no depression and 60 indicates severely depressed.	Baseline, Week 3	No
Secondary	Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Week 3	HAM-A is a clinician-rated 14 item scale that provides an overall measure of global anxiety, including psychic (mental agitation and psychological distress) and somatic (physical complaints related to anxiety) symptoms. Each item was scored on a scale ranging from 0 (not present) to 4 (very severe) with a total score range of 0 to 56, where higher score indicates greater anxiety.	Baseline, Week 3	No
Secondary	Change From Baseline in ADHD Impact Module - Adults (AIM-A) Subscale Score at Week 3	AIM-A: 66 item questionnaire completed by the participant to assess the impact of ADHD on the participant's quality of life. It is comprised of 4 global quality of life (QoL) items (current quality of life item [CQoLI], range:1 to 10; global limitation item [GLI]: range:1 to 4, on the right track item [RTI], range:1 to 3, more good days [GD] than bad days [BD], range:1 to 5, higher scores indicate a better QoL for all the 4 QoL items) and 6 multi-item subscales (living with ADHD, general well-being, performance and daily functioning [PDF], relationships and communication [R/C], Impact of symptoms-bother/concern [IS-B/C] scale, and impact of symptoms-interference [IS-I] scale). Participants responded to each item of multi-item subscale using a likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). Multi-item subscale scores were calculated as an average of scores for the contributing items and transformed into 0 to 100 score where higher scores indicate a better QoL.	Baseline, Week 3	No
Secondary	Change From Baseline in Adult ADHD Quality of Life Scale (AAQOL) Subscale Score at Week 3	AAQoL is a 29-item questionnaire consisting of 4 subscales: life productivity (11 items), psychological health ([PH] 6 items), life outlook (7 items) and relationships (5 items). Participants rated each item on a scale ranging from 1 (not at all/never) to 5 (extremely/very often). The scores of each item were then transformed to a 0 to 100 point scale, higher scores indicating better quality of life. The score for each subscale was calculated as the sum of the corresponding item scores. Total score ranges were: life productivity (0 to 1100), psychological health (0 to 600), life outlook (0 to 700) and relationships (0 to 500), where higher subscale score indicates better quality of life for each subscale.	Baseline, Week 3	No
Secondary	Change From Baseline in Sheehan Disability Scale (SDS) Subscale Scores at Week 3	SDS was a participant-rated questionnaire assessing the effect of the participant's symptoms on the 3 domains/subscales: work/school, social life/leisure activities, and family/home management. Each domain was rated on visual analog scale ranges from 0 to 10 where 0=not at all impaired and 10=extremely impaired, and total SDS score was calculated as a sum of all the domains with a score range of 0=not at all impaired to 30=extremely impaired. Disability scores were reported for each of the domains/subscales. Higher scores reflect greater impairment.	Baseline, Week 3	No

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