Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment

Figures & data

Figure 1. Schematic diagram of (a) the study design and (b) participant disposition.

AWE = adult workplace environment; ITT = intent to treat; MAS = mixed amphetamine salts; PERMP = Permanent Product Measure of Performance; PP = per protocol; V = visit.*Enrolled participants were those for whom all screening assessments were completed and reviewed.

Table 1. Demographics and baseline clinical characteristics, randomized safety population.

	Placebo followed by SHP465 MAS (n = 39)	SHP465 MAS followed by placebo (n = 39)	Total (n = 78)
Mean ± SD age, y	29.7 ± 10.0	28.4 ± 11.0	29.1 ± 10.4
Sex, n (%)
Male	21 (53.8)	22 (56.4)	43 (55.1)
Female	18 (46.2)	17 (43.6)	35 (44.9)
Ethnicity, n (%)
Hispanic or Latino	1 (2.6)	1 (2.6)	2 (2.6)
Not Hispanic or Latino	38 (97.4)	38 (97.4)	76 (97.4)
Race, n (%)
White	35 (89.7)	32 (82.1)	67 (85.9)
Black/African American	1 (2.6)	1 (2.6)	2 (2.6)
Native Hawaiian/Pacific Islander	1 (2.6)	0	1 (1.3)
Asian	1 (2.6)	1 (2.6)	2 (2.6)
American Indian/Alaska Native	0	2 (5.1)	2 (2.6)
Other	1 (2.6)	3 (7.7)	4 (5.1)
Mean ± SD weight, lb	166.0 ± 34.0	160.5 ± 29.7	163.2 ± 31.9
Mean ± SD ADHD diagnosis duration, y	5.1 ± 8.0	6.2 ± 8.8	5.6 ± 8.4
Mean ± SD age at ADHD onset, y	5.5 ± 0.6	5.3 ± 0.7	5.4 ± 0.6
ADHD subtype, n (%)
Inattentive	12 (30.8)	12 (30.8)	24 (30.8)
Hyperactive/impulsive	1 (2.6)	0	1 (1.3)
Combined	26 (66.7)	27 (69.2)	53 (67.9)
Mean ± SD ADHD-RS-IV scores
Total	39.3 ± 10.7	38.2 ± 10.8	38.7 ± 10.7
Hyperactivity/impulsivity subscale	17.8 ± 7.8	16.7 ± 7.9	17.3 ± 7.8
Inattentiveness subscale	21.4 ± 4.4	21.5 ± 4.2	21.5 ± 4.3
Mean ± SD ADHD-SRS scores^a
Total	28.2 ± 8.3	28.2 ± 11.3	28.2 ± 9.9
Hyperactivity/impulsivity subscale	13.5 ± 4.7	13.3 ± 6.2	13.4 ± 5.5
Inattentiveness subscale	14.7 ± 4.9	14.9 ± 6.3	14.8 ± 5.6
PERMP pretest level of difficulty, n (%)
Basic	0	0	0
Easy	2 (5.1)	0	2 (2.6)
Moderate	15 (38.5)	25 (64.1)	40 (51.3)
Difficult	22 (56.4)	14 (35.9)	36 (46.2)

ADHD: attention-deficit/hyperactivity disorder; ADHD-RS-IV: ADHD Rating Scale IV; ADHD-SRS: ADHD self-rating scale; MAS: mixed amphetamine salts; PERMP: Permanent Product Measure of Performance; SD: standard deviation.

^aAt orientation (visit 3).

Table 2. LS mean (95% CI) and P values for treatment differences in PERMP^a, Co-ADHD-RS TSRS^b, and ADHD-SRS^b.

	LS Mean (95% CI) treatment difference	P Value^c	LS Mean (95% CI) treatment difference	P Value^c	LS Mean (95% CI) treatment difference	P Value^c
	PERMP (Total)		PERMP (Number attempted)		PERMP (Number correct)
ITT Population
2–16 h postdose	19.29 (10.95, 27.63)	<0.0001	9.86 (5.68, 14.04)	<0.0001	9.43 (5.26, 13.60)	<0.0001
2 h postdose	10.26 (–1.25, 21.77)	0.0798	5.41 (–0.31, 11.13)	0.0634	4.85 (–0.97, 10.68)	0.1012
4 h postdose	16.75 (4.43, 29.07)	0.0084	8.92 (2.65, 15.19)	0.0059	7.83 (1.75, 13.91)	0.0123
8 h postdose	24.86 (13.40, 36.32)	<0.0001	12.42 (6.69, 18.15)	<0.0001	12.44 (6.68, 18.20)	<0.0001
12 h postdose	23.68 (12.78, 34.58)	<0.0001	11.87 (6.39, 17.35)	<0.0001	11.81 (6.37, 17.24)	<0.0001
14 h postdose	17.11 (6.27, 27.94)	0.0024	9.05 (3.65, 14.46)	0.0013	8.05 (2.59, 13.52)	0.0045
16 h postdose	23.45 (12.54, 34.37)	<0.0001	11.68 (6.25, 17.12)	<0.0001	11.77 (6.27, 17.27)	<0.0001
PP Population
2–16 h postdose	19.94 (10.38, 29.50)	0.0001	10.19 (5.41, 14.98)	<0.0001	9.75 (4.95, 14.54)	0.0002
2 h postdose	8.59 (–3.67, 20.86)	0.1659	4.59 (–1.54, 10.72)	0.1395	4.01 (–2.17, 10.18)	0.1993
4 h postdose	15.02 (0.58, 29.46)	0.0417	8.18 (0.79, 15.57)	0.0307	6.84 (–0.24, 13.93)	0.0581
8 h postdose	26.52 (13.34, 39.70)	0.0002	13.21 (6.55, 19.87)	0.0002	13.31 (6.75, 19.87)	0.0002
12 h postdose	26.31 (13.25, 39.37)	0.0002	13.21 (6.66, 19.76)	0.0002	13.11 (6.57, 19.64)	0.0002
14 h postdose	20.93 (7.81, 34.04)	0.0023	10.96 (4.44, 17.48)	0.0014	9.97 (3.33, 16.61)	0.0039
16 h postdose	22.27 (12.43, 32.12)	<0.0001	11.03 (6.18, 15.87)	<0.0001	11.25 (6.21, 16.28)	<0.0001
	Co-ADHD-RS TSRS (Total)		Co-ADHD-RS TSRS (Hyperactivity/Impulsivity)		Co-ADHD-RS TSRS (Inattentiveness)
ITT Population
2–16 h average postdose	–0.99 (–2.09, 0.11)	0.0783	–0.56 (–1.24, 0.11)	0.0984	–0.38 (–1.03, 0.26)	0.2397
5.5 h postdose	–0.91 (–2.24, 0.43)	0.1796	–0.60 (−1.41, 0.22)	0.1479	–0.32 (–1.25, 0.62)	0.5003
11 h postdose	–0.65 (–2.05, 0.75)	0.3594	–0.33 (–1.11, 0.45)	0.3992	–0.31 (–1.25, 0.64)	0.5207
16.5 h postdose	–1.39 (–2.64, –0.14)	0.0301	–0.78 (–1.59, 0.03)	0.0596	–0.58 (–1.44, 0.28)	0.1830
PP Population
2–16 h average postdose	–1.12 (–2.38, 0.14)	0.0807	–0.72 (–1.44, 0.01)	0.0525	–0.36 (–1.13, 0.41)	0.3506
5.5 h postdose	–0.84 (–2.31, 0.63)	0.2561	–0.65 (–1.50, 0.20)	0.1303	–0.19 (–1.18, 0.80)	0.7011
11 h postdose	–0.68 (–2.30, 0.94)	0.4030	–0.38 (–1.18, 0.42)	0.3466	–0.30 (–1.46, 0.86)	0.6039
16.5 h postdose	–1.76 (–3.21, –0.31)	0.0184	–1.13 (–2.07, –0.18)	0.0200	−0.60 (–1.63, 0.43)	0.2495
	ADHD-SRS (Total)		ADHD-SRS (Hyperactivity/Impulsivity)		ADHD-SRS (Inattentiveness)
ITT Population
2–16 h average postdose	–5.76 (–8.09, –3.43)	<0.0001	–2.61 (–3.85, –1.37)	<0.0001	–3.15 (–4.46, –1.85)	<0.0001
5.5 h postdose	–5.83 (–8.56, –3.10)	<0.0001	–2.78 (–4.24, –1.32)	0.0003	–3.06 (–4.57, –1.54)	0.0001
11 h postdose	–6.22 (–8.86, –3.58)	<0.0001	–2.93 (–4.45, –1.41)	0.0003	–3.29 (–4.78, –1.79)	<0.0001
16.5 h postdose	–5.23 (–7.69, –2.76)	<0.0001	–2.10 (–3.40, –0.79)	0.0021	–3.13 (–4.52, –1.74)	<0.0001
PP Population
2–16 h average postdose	–5.22 (–7.99, –2.46)	0.0004	–2.25 (–3.67, –0.83)	0.0024	–2.97 (–4.58, –1.37)	0.0005
5.5 h postdose	–5.40 (–8.50, –2.30)	0.0010	–2.36 (–4.03, –0.69)	0.0065	–3.04 (–4.73, –1.34)	0.0007
11 h postdose	–5.57 (–8.69, –2.45)	0.0007	–2.53 (–4.26, –0.80)	0.0049	–3.04 (–4.90, –1.18)	0.0018
16.5 h postdose	–4.70 (–7.66, –1.73)	0.0025	–1.86 (–3.40, –0.32)	0.0189	–2.84 (–4.54, –1.14)	0.0015

ADHD: attention-deficit/hyperactivity disorder; CI: confidence interval; Co-ADHD-RS TSRS: ADHD clinician ratings based on counselor observations and input during the Time Segment Rating System; ADHD-SRS: ADHD self-rating scale; ITT: intent to treat; LS: least squares; PERMP: Permanent Product Measure of Performance; PP: per protocol; SD: standard deviation.

^aPositive treatment differences favor SHP465 MAS versus placebo.

^bNegative treatment differences favor SHP465 MAS versus placebo.

^cThe prespecified primary efficacy endpoint was the treatment difference on PERMP total score between 25 mg SHP465 MAS versus placebo for the average of all postdose assessments from 2 to 16 h and at each postdose assessment from 2 to 16 h postdose; all other reported P values are nominal (unadjusted) and descriptive.

Figure 2. PERMP number of problems attempted and number of problems answered correctly overall (a and b) from 2 to 16 h postdose on the last day of each treatment period.

MAS = mixed amphetamine salts; PERMP = Permanent Product Measure of Performance; SD = standard deviation.

Figure 3. Co-ADHD-RS TSRS (a–c) and ADHD-SRS (d–f) total and subscale scores.

ADHD = attention-deficit/hyperactivity disorder; Co-ADHD-RS TSRS = ADHD clinician ratings based on counselor observations and input during the Time Segment Rating System; ADHD-SRS = ADHD self-rating scale; MAS = mixed amphetamine salts; SD = standard deviation.

Table 3. Summary of TEAEs, randomized safety population.

	Placebo (n = 76)	25 mg SHP465 MAS (n = 76)
Any TEAE, n (%)	24 (31.6)	47 (61.8)
TEAEs related to study drug	8 (10.5)	41 (53.9)
Severe TEAEs	0	5 (6.6)
TEAEs leading to discontinuation	0	2 (2.6)
Serious TEAEs	0	0
TEAEs in ≥2% of participants in any treatment arm, n (%)
Insomnia	1 (1.3)	19 (25.0)
Decreased appetite	2 (2.6)	17 (22.4)
Dry mouth	0	11 (14.5)
Headache	5 (6.6)	9 (11.8)
Anorexia	0	7 (9.2)
Dysmenorrhea^a	0	1 (2.9)
Upper respiratory tract infection	2 (2.6)	2 (2.6)
Fatigue	5 (6.6)	1 (1.3)
Dyspepsia	2 (2.6)	1 (1.3)
Nausea	2 (2.6)	0
Pharyngolaryngeal pain	2 (2.6)	0

MAS: mixed amphetamine salts; TEAE: treatment-emergent adverse event.

^aPercentage based on the number of female participants (n = 35).

Table 4. Summary of vital signs at baseline and during each treatment arm, randomized safety population.

		Placebo				25 mg SHP465 MAS
			Hours Postdose				Hours Postdose
	Baseline^a (n = 78)	Predose (n = 74)	4 (n = 75)	8 (n = 75)	16 (n = 75)	Predose (n = 73)	4 (n = 73)	8 (n = 73)	16 (n = 73)
Systolic blood pressure, mmHg
Mean ± SD value	117.9 ± 11.3	119.5 ± 10.5	118.2 ± 11.3	117.2 ± 11.8	120.3 ± 12.0	116.9 ± 10.9	119.9 ± 11.5	120.8 ± 11.8	122.2 ± 10.4
Mean ± SD change from baseline	–	1.7 ± 10.1	0.5 ± 10.3	–0.5 ± 11.2	2.6 ± 11.2	–1.0 ± 8.3	2.0 ± 9.7	2.9 ± 9.4	4.3 ± 11.1
Diastolic blood pressure, mmHg
Mean ± SD value	72.3 ± 9.1	72.5 ± 8.0	71.4 ± 7.5	71.0 ± 8.4	73.3 ± 8.0	72.6 ± 7.3	73.3 ± 8.2	73.7 ± 7.4	75.3 ± 7.9
Mean ± SD change from baseline	–	0.4 ± 9.4	–0.7 ± 8.0	–1.1 ± 8.5	1.1 ± 7.6	0.4 ± 8.2	1.1 ± 8.3	1.5 ± 8.0	3.1 ± 8.0
Pulse, bpm
Mean ± SD value	70.9 ± 11.1	77.7 ± 13.0	74.1 ± 13.2	76.3 ± 11.6	74.3 ± 11.2	78.1 ± 10.3	74.4 ± 9.9	78.5 ± 10.4	77.0 ± 11.5
Mean ± SD change from baseline	–	7.0 ± 13.8	3.4 ± 11.5	5.5 ± 10.7	3.5 ± 12.6	7.6 ± 9.5	3.9 ± 9.7	8.0 ± 10.3	6.5 ± 13.4

MAS: mixed amphetamine salts; SD: standard deviation.

^aThe screening value was used if the baseline value was missing.