Safety and Efficacy Study of SHP465 in Adults Aged 18-55 Years With Attention-deficit/ Hyperactivity Disorder (ADHD)

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02604407
• Collaborator: (none)
• Enrollment: 275
• Locations: 45
• Arms: 3
• Actual Duration (Months): 4.1
• Patients Per Site: 6.1
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The study is designed to evaluate the efficacy and safety of each dose of SHP465 (12.5 and 37.5 mg) given to participants daily in the morning compared to placebo in the treatment of adults aged 18 to 55 years diagnosed with ADHD.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder (ADHD)	Drug: SHP465 12.5mg capsules (one capsule daily); Other: Placebo; Drug: SHP465 12.5mg, 25mg, or 37.5mg capsules (one capsule daily)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 275 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Forced-dose Titration, Safety and Efficacy Study of SHP465 in Adults Aged 18-55 Years With Attention-deficit/ Hyperactivity Disorder (ADHD)
• Actual Study Start Date: Nov 19, 2015
• Actual Primary Completion Date: Mar 24, 2016
• Actual Study Completion Date: Mar 24, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SHP465 12.5 mg Subjects will receive SHP465 12.5 mg	Drug: SHP465 12.5mg capsules (one capsule daily); one capsule daily
Experimental: SHP465 37.5 mg Subjects will receive SHP465 titrated up to 37.5 mg	Drug: SHP465 12.5mg, 25mg, or 37.5mg capsules (one capsule daily); One capsule daily
Placebo Comparator: Placebo Subjects will receive matching placebo	Other: Placebo; Matching placebo capsule that appears identical in size, weight, shape, and color (one capsule daily)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) [Baseline, Visit 6 (Week 4)]

   The ADHD-RS was developed to measure the behaviors of children with Attention deficit hyperactivity disorder (ADHD). The adult ADHD-RS with prompts consists of 18 items designated to reflect current symptomatology of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), with the total score for the rating scale ranging from 0 to 54. Higher score = more severe symptoms.The scale is subdivided into 2 subscales of 9 symptoms each: hyperactivity/impulsivity and inattentiveness. Adult prompts are included with the ADHD-RS to create a semistructured measurement that allows the clinician to probe the extent, frequency, breadth, severity, and consequences of these symptoms to ascertain impairment in an adult population.

Secondary Outcome Measures

1. Clinical Global Impression of Improvement (CGI-I) Score at Visit 6 (Week 4) [Visit 6 (Week 4)]

   CGI scales permit a global evaluation of the participant's severity and improvement over time. CGI-I was performed to rate the severity of a participant's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subject must be 18-55 years of age

Subject is able to provide written, personally signed and dated informed consent.

Subject is willing and able to comply with all of the testing and requirements defined in the protocol

Subject, who is a female, must not be pregnant.

Subject must have a satisfactory medical assessment with no clinically significant or relevant abnormalities.

Subject has a primary diagnosis of ADHD.

Subject has an adult ADHD-RS with prompts total score ≥28 at the baseline visit.

Subject must have a minimum level of intellectual functioning, as determined by the investigator.

Subject is able to swallow a capsule.

Subject is currently not on ADHD therapy or is not completely satisfied with any aspect of their current ADHD therapy.

Exclusion Criteria:

Subject has a current, comorbid psychiatric diagnosis with significant symptoms.

Subject is considered a suicide risk in the opinion of the investigator

Subject has a body mass index (BMI) of <18.5 kg/m2 at the screening visit.

Subject has a BMI ≥40 kg/m2 at the screening visit.

Subject has a concurrent chronic or acute illness, disability, or other condition.

Subject has a history of seizure, a chronic or current tic disorder, or a current diagnosis of Tourette's disorder.

Subject has a history of moderate to severe hypertension.

Subject has a known history of symptomatic cardiovascular disease

Subject has a known family history of sudden cardiac death or ventricular arrhythmia.

Subject has any clinically significant ECG or clinically significant laboratory abnormality at the screening visit.

Subject has current abnormal thyroid function

Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.

Subject has failed to respond, to an adequate course(s) of amphetamine therapy.

Subject has a history of suspected substance abuse or dependence disorder.

Subject has a positive urine drug result at the screening visit (with the exception of subject's current stimulant therapy, if any) or Subject has taken another investigational product or has taken part in a clinical study within 30 days prior to the screening visit.

Subject has previously completed, has discontinued, or was withdrawn from this study.

Subject is taking any medication that is excluded or has not been appropriately washed out according to the protocol requirements.

Subject is required to take or anticipates the need to take medications that have CNS effects or affect performance.

Subject is female and is pregnant or lactating.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pharmacology Research Institute	Encino	California	United States	91316
2	Pharmacology Research Institute (Pri)	Los Alamitos	California	United States	90720
3	Pharmacology Research Institute (Pri)	Newport Beach	California	United States	92660
4	Nrc Research Institute	Orange	California	United States	92868
5	Elite Clinical Trials	Wildomar	California	United States	92595
6	McB Clinical Research	Colorado Springs	Colorado	United States	80910
7	Florida Clinical Research Center Llc	Bradenton	Florida	United States	32401
8	Gulfcoast Clinical Research Center	Fort Myers	Florida	United States	33912
9	Sarkis Clinical Trials	Gainesville	Florida	United States	32607
10	Clinical Neuroscience Solutions, Inc	Jacksonville	Florida	United States	32256
11	Florida Clinical Research Center, Llc	Maitland	Florida	United States	32751
12	Qps Mra, Llc	Miami	Florida	United States	33143
13	Medical Research Group of Central Florida	Orange City	Florida	United States	32763
14	Clinical Neuroscience Solutions, Inc	Orlando	Florida	United States	32801
15	Northwest Behavioral Research Center	Marietta	Georgia	United States	30060
16	Capstone Clinical	Libertyville	Illinois	United States	60048
17	Baber Research Group, Inc	Naperville	Illinois	United States	60563
18	Psychiatric Associates	Overland Park	Kansas	United States	66211
19	Louisiana Research Associates, Inc.	New Orleans	Louisiana	United States	70114
20	Rochester Center For Behavioral Medicine	Rochester Hills	Michigan	United States	48307
21	Clinical Neurophysiology Services	Sterling Heights	Michigan	United States	48314
22	Psychiatric Care and Research Center	O'Fallon	Missouri	United States	63368
23	Midwest Research Group	Saint Charles	Missouri	United States	63304
24	Premier Psychiatric Research Institutute	Lincoln	Nebraska	United States	68526
25	Center For Psychiatry and Behavioral Medicine, Inc	Las Vegas	Nevada	United States	89128
26	Princeton Medical Institute	Princeton	New Jersey	United States	08540
27	Bioscience Research Llc	Mount Kisco	New York	United States	10549
28	Nyu Langone Medical Center	New York	New York	United States	10016
29	Richard H Weisler, Md, Pa & Associates	Raleigh	North Carolina	United States	27609
30	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
31	Ips Research Company	Oklahoma City	Oklahoma	United States	73103
32	Oregon Center For Clinical Investigations, Inc	Portland	Oregon	United States	97214
33	Oregon Center For Clinical Investigations	Salem	Oregon	United States	97301
34	Omega Medical Research	Warwick	Rhode Island	United States	02886
35	Rainbow Research, Inc.	Barnwell	South Carolina	United States	29812
36	Coastal Carolina Research	Mount Pleasant	South Carolina	United States	29464
37	Clinical Neuroscience Solutions	Memphis	Tennessee	United States	38119
38	Futuresearch Trials of Dallas, Lp	Dallas	Texas	United States	75231
39	Bayou City Research, Ltd	Houston	Texas	United States	77007
40	Red Oak Psychiatry Associates	Houston	Texas	United States	77090
41	Houston Clinical Trials, Llc	Houston	Texas	United States	77098
42	Research Across America	Plano	Texas	United States	75093
43	Neuroscience, Inc	Herndon	Virginia	United States	20170
44	Eastside Therapeutic Resource	Kirkland	Washington	United States	98033
45	Summit Research Network (Seattle) Llc	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02604407
• Other Study ID Numbers: SHP465-306
• First Posted: Nov 13, 2015
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity

Study Results

Participant Flow

Recruitment Details	The study was conducted at 43 study centers in the United States between 19 November 2015 and 24 March 2016.
Pre-assignment Detail	A total of 369 participants were screened and 275 participants were enrolled in the study.

Arm/Group Title	Placebo	SHP465 12.5 mg	SHP465 37.5 mg
Arm/Group Description	Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	Participants received SHP465 capsule 12.5 milligram (mg) orally once daily for 4 weeks.	Participants received SHP465 capsule of 12.5 mg during week 1 and 25 mg at week 2 followed by 37.5 mg at weeks 3 and 4 orally once daily.
Period Title: Overall Study
STARTED	91	92	92
TREATED	89	92	90
COMPLETED	80	80	76
NOT COMPLETED	11	12	16

Baseline Characteristics

Arm/Group Title	Placebo	SHP465 12.5 mg	SHP465 37.5 mg	Total
Arm/Group Description	Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	Participants received SHP465 capsule 12.5 mg orally once daily for 4 weeks.	Participants received SHP465 capsule of 12.5 mg during week 1 and 25 mg at week 2 followed by 37.5 mg at weeks 3 and 4 orally once daily.	Total of all reporting groups
Overall Participants	89	92	90	271
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.5 (10.77)	33 (10.40)	32.4 (10.02)	33.3 (10.40)
Sex: Female, Male (Count of Participants)
Female	47 52.8%	35 38%	39 43.3%	121 44.6%
Male	42 47.2%	57 62%	51 56.7%	150 55.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4)
Description	The ADHD-RS was developed to measure the behaviors of children with Attention deficit hyperactivity disorder (ADHD). The adult ADHD-RS with prompts consists of 18 items designated to reflect current symptomatology of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), with the total score for the rating scale ranging from 0 to 54. Higher score = more severe symptoms.The scale is subdivided into 2 subscales of 9 symptoms each: hyperactivity/impulsivity and inattentiveness. Adult prompts are included with the ADHD-RS to create a semistructured measurement that allows the clinician to probe the extent, frequency, breadth, severity, and consequences of these symptoms to ascertain impairment in an adult population.
Time Frame	Baseline, Visit 6 (Week 4)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all participants in the safety set who had at least 1 post dose baseline primary efficacy assessment (ADHD-RS with prompt total score) on treatment.

Arm/Group Title	Placebo	SHP465 12.5 mg	SHP465 37.5 mg
Arm/Group Description	Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	Participants received SHP465 capsule 12.5 mg orally once daily for 4 weeks.	Participants received SHP465 capsule of 12.5 mg during week 1 and 25 mg at week 2 followed by 37.5 mg at weeks 3 and 4 orally once daily.
Measure Participants	86	89	88
Baseline	40.5 (6.52)	39.8 (6.38)	39.9 (7.07)
Change at Visit 6	-11.0 (11.47)	-18.1 (13.42)	-23.8 (11.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SHP465 12.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed-effects model for repeated measure
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	-8.1
	Confidence Interval	(2-Sided) 95%; -11.7 to -4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Between treatment groups of SHP465 12.5 mg and Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SHP465 37.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed-effects model for repeated measure
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Mean
	Estimated Value	-13.4
	Confidence Interval	(2-Sided) 95%; -17.1 to -9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Between treatment groups of SHP465 37.5 mg and Placebo.

2. Secondary Outcome

Title	Clinical Global Impression of Improvement (CGI-I) Score at Visit 6 (Week 4)
Description	CGI scales permit a global evaluation of the participant's severity and improvement over time. CGI-I was performed to rate the severity of a participant's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame	Visit 6 (Week 4)

Outcome Measure Data

Analysis Population Description

Full-analysis set (FAS) consisted of all participants in the safety set who had at least 1 postdose baseline primary efficacy assessment (ADHD-RS with prompt total score) on treatment with number of participants evaluable for this outcome.

Arm/Group Title	Placebo	SHP465 12.5 mg	SHP465 37.5 mg
Arm/Group Description	Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	Participants received SHP465 capsule 12.5 mg orally once daily for 4 weeks.	Participants received SHP465 capsule of 12.5 mg during week 1 and 25 mg at week 2 followed by 37.5 mg at weeks 3 and 4 orally once daily.
Measure Participants	77	78	73
Mean (Standard Deviation) [Units on a scale]	3.1 (1.05)	2.4 (1.16)	1.9 (1.10)

Adverse Events

Time Frame	From the Start of Study Drug Administration up to Follow-up (Week 5)
Arm/Group Title	Placebo		SHP465 12.5 mg		SHP465 37.5 mg
Arm/Group Description	Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.		Participants received SHP465 capsule 12.5 milligram (mg) orally once daily for 4 weeks.		Participants received SHP465 capsule of 12.5 mg during week 1 and 25 mg at week 2 followed by 37.5 mg at weeks 3 and 4 orally once daily.
All Cause Mortality
	Placebo		SHP465 12.5 mg		SHP465 37.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		SHP465 12.5 mg		SHP465 37.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/89 (0%)		0/92 (0%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		SHP465 12.5 mg		SHP465 37.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/89 (13.5%)		44/92 (47.8%)		49/90 (54.4%)
Gastrointestinal disorders
Dry mouth	3/89 (3.4%)	3	13/92 (14.1%)	13	20/90 (22.2%)	20
Metabolism and nutrition disorders
Decreased appetite	4/89 (4.5%)	4	18/92 (19.6%)	18	27/90 (30%)	27
Nervous system disorders
Headache	4/89 (4.5%)	4	6/92 (6.5%)	6	11/90 (12.2%)	11
Psychiatric disorders
Anxiety	1/89 (1.1%)	1	6/92 (6.5%)	7	4/90 (4.4%)	4
Bruxism	0/89 (0%)	0	1/92 (1.1%)	1	5/90 (5.6%)	5
Initial insomnia	1/89 (1.1%)	1	4/92 (4.3%)	4	6/90 (6.7%)	6
Insomnia	1/89 (1.1%)	1	12/92 (13%)	12	10/90 (11.1%)	13
Irritability	0/89 (0%)	0	5/92 (5.4%)	6	3/90 (3.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.