NCT01081132

Dose-optimization in Adolescents Aged 13-17 Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD) Using Extended-release Guanfacine HCl

Completed Phase 3 Results posted Last updated 28 June 2021

What this trial tests

Phase 3 trial testing Extended-release Guanfacine Hydrochloride in Attention-Deficit/Hyperactivity Disorder in 314 participants. Completed in 16 May 2013.

Timeline

19 September 2011

Primary endpoint
16 May 2013

16 May 2013

Quick facts

Lead sponsor	Shire
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	314
Start date	19 September 2011
Primary completion	16 May 2013
Estimated completion	16 May 2013
Sites	54 locations across United States

Drugs / interventions tested

• Extended-release Guanfacine Hydrochloride
• Placebo

Conditions studied

• Attention-Deficit/Hyperactivity Disorder — all drugs for Attention-Deficit/Hyperactivity Disorder →

Sponsor

Shire — full company profile →

Who can join

Adults 13 to 17, any sex, with Attention-Deficit/Hyperactivity Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 13 Primary · Baseline through week 13

The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.

Group	Value	95% CI
PLACEBO	-18.527	± 1.0841
SPD503	-24.552	± 1.0625

Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale at the Last On-Treatment Assessment Secondary · Baseline through week 13

CGI-S assesses the severity of the subject's condition on a 7-point scale: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill)

Group	Value	95% CI
PLACEBO	36.1
SPD503	50.6

Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Learning and School Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.457	± 0.058
SPD503	-0.572	± 0.058

Change From Baseline in the WFIRS-P Family Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Family Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.314	± 0.055
SPD503	-0.371	± 0.054

Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.376	± 0.051
SPD503	-0.459	± 0.050

Change From Baseline in the WFIRS-P Global Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.296	± 0.036
SPD503	-0.347	± 0.035

Change From Baseline in the WFIRS-P Risk Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Risk Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.194	± 0.027
SPD503	-0.191	± 0.026

Change From Baseline in the WFIRS-P Social Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Social Domain consists of 7-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.234	± 0.046
SPD503	-0.263	± 0.045

Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Child Self-Concept Domain consists of 3-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.376	± 0.067
SPD503	-0.275	± 0.066

Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Life Skills Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.328	± 0.046
SPD503	-0.375	± 0.045

Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 13 Secondary · Baseline and week 13

The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

Group	Value	95% CI
PLACEBO	-0.632	± 0.096
SPD503	-0.841	± 0.096

Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores at the Last On-Treatment Assessment Secondary · weeks 1 through 13

Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

Group	Value	95% CI
PLACEBO	45.8
SPD503	67.5

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PLACEBO

Serious: 2/155 (1%)

Deaths: —

SPD503

Serious: 4/157 (3%)

Deaths: —

Serious adverse events (10 terms)

Reaction	System	PLACEBO	SPD503
Abdominal pain	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Cholecystitis chronic	Hepatobiliary disorders	—	—
Clavicle fracture	Injury, poisoning and procedural complications	—	—
Concussion	Injury, poisoning and procedural complications	—	—
Pelvic fracture	Injury, poisoning and procedural complications	—	—
Loss of consciousness	Nervous system disorders	—	—
Homicidal ideation	Psychiatric disorders	—	—
Ovarian cyst ruptured	Reproductive system and breast disorders	—	—
Withdrawal hypertension	Vascular disorders	—	—

Other adverse events (19 terms — click to expand)

Reaction	System	PLACEBO	SPD503
Somnolence	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Dizziness	Nervous system disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Sedation	Nervous system disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Increased appetite	Metabolism and nutrition disorders	—	—
Insomnia	Psychiatric disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Irritability	General disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Dizziness postural	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: Abdominal pain, Vomiting, Cholecystitis chronic, Clavicle fracture, Concussion, Pelvic fracture, Loss of consciousness, Homicidal ideation.

Data from ClinicalTrials.gov NCT01081132 adverse events section.

Sponsor's own description

To assess the efficacy of optimized Extended-release Guanfacine Hydrochloride compared with placebo in the treatment of adolescents aged 13-17 years with a diagnosis of ADHD as measured by the ADHD-RS-IV

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.
   Wilens TE, Robertson B, Sikirica V, Harper L, et al · · 2015 · cited 39× · PMID 26506582 · DOI 10.1016/j.jaac.2015.08.016
2. Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison.
   Joseph A, Ayyagari R, Xie M, Cai S, et al · · 2017 · cited 23× · PMID 28258319 · DOI 10.1007/s00787-017-0962-6
3. Efficacy and Tolerability of Different Interventions in Children and Adolescents with Attention Deficit Hyperactivity Disorder.
   Luan R, Mu Z, Yue F, He S. · · 2017 · cited 8× · PMID 29180967 · DOI 10.3389/fpsyt.2017.00229
4. Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses.
   Coghill DR, Werner-Kiechle T, Farahbakhshian S, Bliss C, et al · · 2021 · cited 7× · PMID 32691164 · DOI 10.1007/s00787-020-01586-5
5. A simple formula for enumerating comparisons in trials and network meta-analysis.
   Shokraneh F, Adams CE. · · 2019 · cited 2× · PMID 30863537 · DOI 10.12688/f1000research.17352.2