Significant

Symptom
Reduction

Demonstrated improvement in ADHD symptoms vs placebo as measured by ADHD-RS-IV total score and CGI-I1-7

Twice the reduction in ADHD-RS-IV total score1-7

Dose Optimization: Study 301

Primary Endpoint: Twice the reduction in ADHD symptoms vs placebo as measured by ADHD-RS-IV total score.2,3

ADHD-RS-IV Total Score Change at Endpoint (ITT Population)

In dose optimization clinical Study 301 adult patients treated with Mydayis showed 2 times more reduction in ADHD-RS-IV total score

ADHD-RS-IV is an 18-item scale that was developed to measure the behaviors of children with ADHD. In this study, adult prompts were included to allow the clinician to probe the extent of symptoms in an adult population. Symptom severity is rated on a four-point scale, ranging from 0 (none) to 3 (severe).

Similar reductions were observed in multiple studies

In Study 1, adult patients treated with Mydayis 37.5 mg demonstrated more than twice the improvement in ADHD-RS total score from baseline to Week 4 compared to placebo-treated adult patients.
(LS mean change of –23.8, –18.5, and –10.4 for Mydayis 37.5 mg (n=88), Mydayis 12.5 mg (n=89), and placebo (n=86), respectively; P <0.001 vs placebo.)1,4,5

In controlled Study 303, there was a two-fold greater improvement in ADHD-RS-IV total scores from baseline to endpoint in Mydayis-treated patients vs placebo-treated adult patients.
(LS mean change –19.7, –18.9, –9.1 for Mydayis 50 mg (n=101), Mydayis 25 mg (n=103), and placebo (n=103), respectively; P <0.0001 vs placebo.)6,7


Improved efficacy VS PLACEBO1,4,5

Forced-dose Titration: Study 1

Primary Endpoint: Change in mean ADHD Rating Scale (ADHD-RS) total score at Week 4.

ADHD-RS Total Score Change at Endpoint (Week 4, Full Analysis Set)

ADHD-RS rating scale with adult prompts – change at endpoint (week 4, full analysis set)

The study was not designed to make comparisons between the Mydayis 12.5 mg and 37.5 mg treatment arms.

The effect size indicates the magnitude of the difference in treatment effect between the placebo and Mydayis treatment groups. An effect size of 0.2 is considered small, 0.5 is medium, and 0.8 is large.8

The effect size for Mydayis vs placebo was 0.67 in 12.5 mg and 1.11 in 37.5 mg

The study was not designed to make comparisons between Mydayis 12.5 mg and 37.5 mg treatment arms.

The effect size was calculated as difference in LS mean (Mydayis dose minus placebo) divided by the estimated standard deviation.4,5

IMPORTANT SAFETY INFORMATION (continued)

Warnings and Precautions (continued)

  • CNS stimulants cause increased blood pressure (mean increase ~2-4 mm Hg) and heart rate (mean increase ~3-6 bpm). Monitor for tachycardia and hypertension.
  • Exacerbation of Pre-existing Psychosis : May exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder : May induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, or a family history of suicide, bipolar disorder, and depression). New Psychotic or Manic Symptoms : At recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients with no prior history of psychotic illness or mania. Discontinue if symptoms occur.

Clinicians saw improved ADHD Symptoms by CGI-I1,4,5

Forced-dose Titration: Study 1

Key Secondary Endpoint: CGI-I scores at week 4 were significantly lower for patients treated with Mydayis vs patients receiving placebo (P <0.001). LS mean CGI-I scores were 1.9, 2.4, and 3.1 in the groups treated with Mydayis 37.5 mg (n=90), Mydayis 12.5 mg (n=92), and placebo (n=89), respectively (1=very much improved, 7=very much worse).4,5

In another assessment of the CGI-I, more than twice as many adult patients on Mydayis were considered “very much improved” or “much improved” when symptom severity vs placebo was rated by clinicians.5

Patients with Improvement at Endpoint (ITT Population)

In forced-dose titration clinical Study 1 for Mydayis (mixed salts of a single-entity amphetamine product) more patients improved on Mydayis vs placebo based on CG-I

The study was not designed to make comparisons between Mydayis 12.5 mg and 37.5 mg treatment arms.

CGI-I assesses global improvement in a patient’s overall condition since baseline. Ratings are based on a seven-point scale: 1 (very much improved) to 7 (very much worse).4


Phase 3: Study Designs

  • Study 1
  • 301
  • 303
  • 304

Dose Optimization: Study 301

Dose optimization clinical Study 301 for Mydayis (mixed salts of a single-entity amphetamine product) study design

PRIMARY ENDPOINT: Change in mean ADHD Rating Scale-IV (ADHD-RS-IV) total score at endpoint.

Optimized=at least a 30% decrease from baseline in patient’s ADHD-RS-IV score and tolerable side effects.2 The mean daily dose was 34.7 mg.3

Mydayis 62.5 mg and 75 mg are not approved doses.
AIM-A=Adult ADHD Impact Module

POPULATION

274 adults, aged 18-55, who met DSM-IV-TR® criteria for ADHD

DESIGN

Randomized, double-blind, multicenter, placebo-controlled, dose-optimization, parallel-group study

DSM-IV-TR®=Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision.

DSM-IV-TR is a registered trademark of the American Psychiatric Association.

Forced-dose Titration: Study 303

Forced-dose titration clinical Study 303 for Mydayis (mixed salts of a single-entity amphetamine product) study design

PRIMARY ENDPOINT: Change in mean ADHD Rating Scale-IV (ADHD-RS-IV) total score at endpoint.6,7

A group of 102 patients treated with Mydayis 75 mg (1.5 times the maximum adult dose) is not shown here.6,7

POPULATION

411 adults, aged 18-55, who met DSM-IV-TR® criteria for ADHD were in the randomized safety population

DESIGN

Forced-dose titration, randomized, double-blind, multicenter, parallel-group, placebo-controlled study

DSM-IV-TR®=Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision.

DSM-IV-TR is a registered trademark of the American Psychiatric Association.

Open-label: Study 304

Open-label clinical Study 304 for Mydayis (mixed salts of a single-entity amphetamine product) study design

PRIMARY ENDPOINT: Evaluate long-term safety.9

POPULATION

505 adults, aged 18-55, who met DSM-IV-TR® criteria for ADHD

DESIGN

Single-arm, open-label, multicenter, long-term safety study

DSM-IV-TR®=Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision.

DSM-IV-TR is a registered trademark of the American Psychiatric Association.

Forced-dose Titration: Study 1

Forced-dose titration clinical Study 1 for Mydayis (mixed salts of a single-entity amphetamine product) study design

PRIMARY ENDPOINT: Change in mean ADHD Rating Scale with Adult Prompts (ADHD-RS-AP) total score at endpoint.1,4,5

Secondary Endpoint: Change in CGI-I at endpoint.1,4,5

Patients receiving active treatment were initiated with Mydayis 12.5 mg. One group received Mydayis 12.5 mg throughout the 4 weeks. A second group was titrated weekly up to 37.5 mg by week 3.1,4,5

CGI-I=Clinical Global Impression-Improvement

POPULATION

275 adults, aged 18-55, who met DSM-5® criteria for ADHD

DESIGN

Forced-dose titration, randomized, double-blind, multicenter, parallel-group, placebo-controlled study

DSM-5®=Diagnostic and Statistical Manual of Mental Disorders, 5th edition.

DSM-5 is a registered trademark of the American Psychiatric Association.

References
  1. Mydayis [package insert]. Lexington, MA; Shire US Inc.
  2. Spencer TJ, Adler LA, Weisler RH, Youcha SH. Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study. J Clin Psychiatry. 2008;69(9):1437-1448.
  3. Data on file; SPD465-301; Shire US Inc.
  4. Weisler RH, Greenbaum M, Arnold V, et al. Efficacy and safety of SPD465 mixed amphetamine salts in the treatment of attention-deficit/hyperactivity disorder in adults: results of a randomized, double-blind, placeo-controlled, forced-dose clinical study. CNS Drugs. 2017;31:685-697.
  5. Data on file; SPD465-306; Shire US Inc.
  6. Data on file; SPD465-303; Shire US Inc.
  7. Frick G, Yan B, Adler LA. Triple-bead mixed amphetamine salts (SPD465) in adults with ADHD: results of a phase 3, double-blind, randomized, forced-dose trial. J Atten Disord. 2017; doi:10.1177/1087054717696771.
  8. Cohen, J. (1988), Statistical Power Analysis for the Behavioral Sciences, 2nd Edition. Hillsdale, N.J.: Lawrence Erlbaum.
  9. Adler LA, Frick G, Yan B. A long-term, open-label, safety study of triple-bead mixed amphetamine salts (SHP465) in adults with ADHD. J Atten Disord. 2017; doi:10.1177/1087054717696770.