VYVANSE CHEWABLE TABLETS CII

Pediatric Patients Ages 6 to 12 Years with ADHD – Studies 1, 2, and 3

Study 1

• The double-blind, randomized, placebo-controlled, parallel-group study included 290 pediatric patients 6 to 12 years with ADHD. Patients were randomly assigned to receive final doses of 30 mg, 50 mg, or 70 mg of Vyvanse or placebo once daily in the morning for 4 weeks total. All patients were initiated on 30 mg during the 1st week, and titrated.

• The primary efficacy outcome was change in Total Score from baseline to endpoint in investigator ratings on the ADHD Rating Scale (ADHD-RS).

• All doses of Vyvanse were found to be superior to placebo in the primary efficacy outcome. The highest dose of 70 mg/day was numerically superior to both lower doses.

Study 2

• The double-blind, placebo-controlled, randomized, crossover design, analog classroom study included 52 pediatric patients 6 to 12 years of age with ADHD. Following a 3­ week open-label dose optimization with Adderall XR, patients were randomly assigned to continue their optimized dose of Adderall XR (10 mg, 20 mg, or 30 mg), Vyvanse (30 mg, 50 mg, or 70 mg), or placebo once daily in the morning for 1 week each treatment.

• Efficacy assessments were conducted at 1, 2, 3, 4.5, 6, 8, 10, and 12 hours post-dose using the Swanson, Kotkin, Agler, M.Flynn, and Pelham Deportment scores (SKAMP-DS).

• There was a significant difference in patient behavior based upon the average of investigator ratings on the SKAMP-DS observed between patients who received Vyvanse vs patients who received placebo.

• Vyvanse achieved statistical significance in drug effect from hours 2 to 12 post-dose.

Study 3

• The second double-blind, placebo-controlled, randomized, crossover design, analog classroom study included 129 pediatric patients 6 to 12 years of age with ADHD. Following a 4-week open-label dose optimization with Vyvanse (30 mg, 50 mg, 70 mg), patients were randomly assigned to continue their optimized dose of Vyvanse or placebo once daily in the morning for 1 week each treatment.

• There was a significant difference in patient behavior based on the average of investigator ratings on the SKAMP-Deportment scores across all 7 assessments conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose observed between patients who received Vyvanse vs patients who received placebo.

Pediatric Patients Ages 13 to 17 Years with ADHD 

Study 4

• The double-blind, randomized, placebo-controlled, parallel-group study included 314 pediatric patients 13 to 17 years of age with ADHD. Patients were randomly assigned 1:1:1:1 to receive either Vyvanse 30 mg, 50 mg, 70 mg, or placebo once daily for 4 weeks. All patients in the Vyvanse arm were initiated on 30 mg for the 1st week.

• The primary efficacy outcome was change in Total Score from baseline to endpoint in investigator ratings on the ADHD Rating Scale (ADHD-RS).

• All Vyvanse dose groups were found to be superior to placebo in the primary efficacy outcome.

Pediatric Patients Ages 6 to 17 Years: Short-Term Treatment in ADHD

Study 5

• The double-blind, randomized, placebo- and active-controlled parallel-group, dose-optimization study included 336 pediatric patients 6 to 17 years of age with ADHD. Patients were randomly assigned 1:1:1 to receive either Vyvanse (30 mg, 50 mg, or 70 mg per day), an active control, or placebo for 8 weeks. During the Dose Optimization Period, subjects were titrated until an optimal dose, based on tolerability and investigator’s judgment, was reached.

• Patients treated with Vyvanse achieved significantly greater efficacy compared with placebo (placebo-adjusted mean reduction in ADHD-RS-IV total score of 18.6).

• Vyvanse also achieved greater improvement on the Clinical Global Impression-Improvement (CGI-I) rating scale compared to subjects on placebo.

Pediatric Patients Ages 6 to 17 Years: Maintenance Treatment in ADHD 

Study 6

• The double-blind, placebo-controlled, randomized withdrawal study included 276 pediatric patients 6 to 17 years of age with ADHD. Patients received open-label Vyvanse for at least 26 weeks prior to being assessed for entry into the randomized withdrawal period. Treatment response was determined based on CGI-S <3 and Total Score on the ADHD-RS ≤22.

• Patients who maintained treatment response for 2 weeks at the end of the open label treatment were eligible to be randomized to ongoing treatment with the same dose of Vyvanse or switched to placebo during the double-blind phase.

• 15.8% of patients treated with Vyvanse had treatment failures compared with 67.5% of patients treated with placebo at the end of the randomized withdrawal period. Treatment failure was defined as at least a 50% increase (worsening) in the ADHD-RS Total Score and at least a 2-point increase in the CGI-S score compared with scores at entry into the double-blind randomized withdrawal phase.

Adults: Short-Term Treatment in ADHD – Studies 7 and 8

Study 7

• The double-blind, randomized, placebo-controlled, parallel-group study included 420 adults 18 to 55 years of age with ADHD. Patients were randomly assigned to receive final doses of Vyvanse 30 mg, 50 mg, or 70 mg or placebo for 4 weeks. In the Vyvanse arm, all patients were initiated on 30 mg for the 1st week.

• The primary efficacy outcome was change in Total Score from baseline to endpoint in investigator ratings on the ADHD Rating Scale (ADHD-RS).

• All dose groups of Vyvanse achieved superiority to placebo in the primary efficacy outcome.

Study 8

• The multi-center, randomized, double-blind, placebo-controlled, cross-over, modified analog classroom study included 142 adults 18 to 55 years of age with ADHD. After a 4-week open-label, dose optimization phase, patients were randomly assigned to 1 of 2 treatment sequences:

• 1) Vyvanse (optimized dose) followed by placebo, each for 1 week, or

• 2) Placebo followed by Vyvanse, each for 1 week.

• Efficacy was assessed using the Permanent Product Measure of Performance (PERMP), a skill-adjusted math test that measures attention in ADHD.

• Vyvanse achieved a statistically significant improvement in attention across all post-dose time points as measured by average PERMP total scores compared with placebo. PERMP assessments were obtained pre-dose (-0.5 hours) and at 2, 4, 8, 10, 12, and 14 hours post-dose.

Adults: Maintenance Treatment in ADHD 

Study 9

• The double-blind, placebo-controlled, randomized withdrawal design study included 123 adults 18 to 55 years of age with ADHD. Eligible patients must have had a minimum of 6 months of Vyvanse treatment and demonstrated treatment response, as defined by CGI-S ≤3 and Total Score on the ADHD-RS <22.

• Patients that maintained treatment response at Week 3 of the open label treatment phase (N=116) were eligible to be randomized to ongoing treatment with the same dose of Vyvanse (N=56) or switched to placebo (N=60) during the double-blind phase. Patients were observed for relapse (treatment failure) during the 6-week double-blind phase.

• Efficacy endpoint was the proportion of patients with treatment failure during the double-blind phase. Treatment failure was defined as at least a 50% increase (worsening) in the ADHD-RS Total Score and at least a 2-point increase in the CGI-S score compared with scores at entry into the double-blind phase.

• 9% of patients treated with Vyvanse had treatment failures compared with 75% of patients treated with placebo at the end of the double-blind phase. 

Binge Eating Disorder (BED) – Studies 10, 11, 12, 13

Study 10

• The randomized, double-blind, parallel-group, placebo-controlled, forced-dose titration phase 2 study compared the efficacy of Vyvanse 30 mg, 50 mg, and 70 mg per day to placebo in reducing the number of binge days per week in adults with at least moderate to severe BED for 11 weeks.

• Vyvanse 30 mg/day did not achieve statistical significance on the primary endpoint compared with placebo.

• Vyvanse 50 mg and 70 mg/day doses met the primary endpoint achieving superiority compared with placebo.

Study 11 and 12

• The two 12-week randomized, double-blind, multi-center, parallel-group, placebo-controlled, dose-optimization studies evaluated the efficacy of Vyvanse for the treatment of BED in adults 18 to 55 years of age with moderate to severe BED. A binge day was defined as a day with at least 1 binge episode, as determined from the patient’s daily binge diary.

• The studies included a 4-week dose-optimization period and an 8-week dose-maintenance period. The primary efficacy outcome was defined as the change from baseline at week 12 in the number of binge days per week.

• Vyvanse achieved a statistically significantly greater reduction from baseline in mean number of binge days per week at week 12 compared with placebo. 

• A greater proportion of patients treated with Vyvanse had improvements on the CGI-I rating scale, 4-week binge cessation, and a greater reduction in the Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) total score.

Study 13

• The double-blind, placebo controlled, randomized withdrawal design study evaluated the maintenance of efficacy based on time to relapse for Vyvanse compared with placebo in 267 adults 18 to 55 years of age with moderate to severe BED.

• Patients were eligible if they responded to the preceding 12-week open-label treatment phase. Patients enrolled were randomly assigned to continue Vyvanse or placebo for up to 26 weeks of observation for relapse.

• Relapse during the double-blind phase was defined as having 2 or more binge days each week for two consecutive weeks (14 days) prior to any visit and having an increase in CGI-S score of 2 or more points compared to the randomized-withdrawal baseline.  

• Vyvanse demonstrated to be superior to placebo as measured by time to relapse.