Table 3.

Subgroup variation in the 4-week change from baseline in early satiety/postprandial fullness subscore between treatment groups using prespecified baseline post-randomization subgroups

Baseline Subgroup§	Adjusted Early satiety/fullness change from baseline to 4-weeks*				Difference of differences (Buspirone -Placebo) (95% CI)†		Interaction P‡
	Buspirone		Placebo
	N	Mean ) (SD)	N	Mean ) (SD)		P
Overall	39	−1.17 (1.19)	39	−1.03 (1.19)	−0.13 (−0.67, 0.41)	0.63
Clinic							0.86
1	10	−0.43	7	−0.75	0.33 (−0.59,1.24)	0.46
2	1	−1.25	2	−0.38	−0.88 (−47.64, 45.89)	0.85
3	11	−1.18	17	−1.13	−0.05 (−1.12,1.03)	0.93
4	0	n/c	0	n/c	n/c	n/c
5	10	−1.87	6	−1.29	−0.61 (−1.98, 0.77)	0.36
6	7	−1.19	7	−0.99	−0.11 (−1.23, 1.02)	0.84
Demographic
Gender
Female	36	−1.08	36	−0.99	−0.10 (−0.61, 0.49)	0.74	0.34
Male	3	−2.17	3	−1.58	−0.58 (−3.49, 2.32)	0.61
Age (years)							0.15
< 50	24	−1.00	24	−1.21	0.21 (−0.53, 0.95)	0.57
≥ 50	15	−1.42	15	−0.76	−0.68 (−1.52, 0.17)	0.11
Race							0.67
White	37	−1.10	34	−0.92	−0.24 (−0.81, 0.34)	0.42
Non-white	2	−1.38	5	−1.80	0.43 (−2.20, 3.05)	0.70
Hispanic Ethnicity							0.80
Hispanic	8	−1.40	15	−1.03	−0.37 (−1.53, 0.78)	0.51
Not Hispanic	31	−1.10	24	−1.03	−0.07 (−0.74, 0.59)	0.83
Clinical
BMI group (kg/m2)							0.43
< 25 (low-normal)	14	−0.75	9	−0.75	0.0 (−1.01, 1.01)	1.00
≥ 25 (overweight/ obese)	25	−1.40	30	−1.12	−0.28 (−0.96, 0.39)	0.40
Etiology							0.09
Diabetic	11	−1.80	18	−1.03	−0.77 (−1.66, 0.12)	0.09
Idiopathic	28	−0.92	21	−1.04	0.12 (−0.61, 0.84)	0.75
Scintigraphic gastric emptying (GES) ¶
Gastric retention							0.25
Delayed retention	19	−1.09	17	−1.40	0.30 (−0.42,1.22)	0.40
Not delayed	20	−1.24	22	−0.75	−0.49 (−1.32, 0.34)	0.24
Intragastric meal distribution
Low	1	−0.75	4	−0.5	−0.25 (−3.73, 3.23)	0.83	0.77
Normal	14	−1.14	18	−1.29	0.15 (−70, −1.85)	0.72
Medication use (prior month)
Antiemetic
Any antiemetic	26	−1.19	19	−1.14	−0.05 (−0.81, 0.72)	0.90	0.66
None	13	−1.12	20	−0.93	−0.19 (−1.07, 0.68)	0.66
Any 5-HT3 receptor agonist	18	−1.25	10	−1.10	−0.15 (−1.22,0.92)	0.78	0.81
No use	21	−1.09	29	−1.01	−0.09 (−0.77, 0.60)	0.80
Prokinetic use	10	−1.38	9	−1.08	−0.29 (−1.79, 1.21)	0.69	0.52
No use	29	−1.09	30	−1.02	−0.08 (−0.67, 0.51)	0.79
Sx modulator (TCA)	4	−0.88	2	−0.50	−0.38 (−2.35, 1.60)	0.63	0.93
No use	35	−1.20	37	−1.06	−0.14 (−0.73, 0.45)	0.64
Proton pump inhibitor use	28	−1.17	25	−1.05	−0.12 (−0.84, 0.59)	0.74	0.79
No use	11	−1.16	14	−1.00	−0.16 (−1.07, 0.75)	0.72
Narcotic use	2	−0.13	3	−2.08	1.95 (−2.42, 6.34)	0.25	0.05
Not used	37	−1.22	36	−0.94	−0.28 (−0.84, 0.28)	0.32
Symptoms
Nausea							0.83
Severe/very severe	26	−1.25	23	−1.04	−0.21 (−0.91, 0.50)	0.56
None to moderate	13	−1.00	16	−1.02	0.02 (−0.95, 0.98)	0.97
Vomiting							0.79
Severe/very severe	8	−1.34	9	−0.94	−0.40 (−1.76, 0.96)	0.54
None to moderate	31	−1.12	30	−1.06	−0.06 (−0.69, 0.56)	0.84
Stomach fullness							0.38
Severe/very severe	33	−1.27	33	−1.02	−0.26 (−0.87, 0.36)	0.41
None to moderate	6	−0.58	6	−1.13	0.54 (−0.81, 1.89)	0.39
Early satiety							0.19
Severe/very severe	25	−1.28	29	−1.31	0.03 (−0.66, 0.72)	0.93
None to moderate	14	−0.96	10	−0.23	−0.74 (−1.59, 0.12)	0.09
Bloating							0.003
Severe/very severe	33	−1.36	26	−0.71	−0.65 (−1.25, −0.05)	0.03
None to moderate	6	−0.08	13	−1.67	1.58 (0.36, 2.82)	0.01
Abdominal pain							0.96
Severe/very severe	17	−1.40	14	−1.21	−0.18 (−1.29, 0.92)	0.74
None to moderate	22	−0.99	25	−0.93	−0.06 (−0.66, 0.54)	0.84
Anxiety & Depression (HADS)							0.90
Any anxiety (8+)	23	−1.29	23	−1.03	−0.26 (−1.00, 0.47)	0.47
No anxiety (<8)	14	−1.05	14	−1.00	−0.05 (−1.05, 0.94)	0.84
							0.53
Any depression (8+)	18	−1.15	15	−1.03	−0.12 (−0.95, 0.71)	0.77
No depression (<8)	19	−1.25	22	−1.01	−0.24 (−1.07, 0.59)	0.56
Water load test							0.19
Low volume (<238 ml)	5	−1.48	5	−0.02	−1.46 (−2.22, −0.70)	0.003
Volume ≥ 238 ml	21	−1.33	23	−1.20	−0.14 (−0.99, 0.72)	0.75
Adherence to prescribed dose ║
Dose by capsule count
Adherent	23	−1.35	29	−1.09	−0.25 (−0.92, 0.41)	0.45	0.72
Non-adherent	10	−0.90	16	−0.86	−0.04 (−1.07, 0.99)	0.94
Dose by ANMS Daily   Diary self-report
Adherent	19	−1.41	21	−1.01	−0.40 (−1.19, 0.39)	0.32	0.22
Non-adherent	10	−71	10	−1.59	0.88 (−0.59, 2.36)	0.22

^*Mean differences adjusted for the baseline value of the outcome and treatment group indicator are the Least Squares means (LS-means) (i.e., the predicted population margins) computed using a generalized linear ANCOVA model of the primary outcome on treatment group and baseline value, and holding independent variables at their means.

^†The mean difference of differences (DoD) between Buspirone and Placebo, 95% confidence interval and P (2-sided) were derived from an ANCOVA, regressing an indicator for treatment group on fullness/early satiety subscore, adjusting for the baseline value of fullness/early satiety subscore, within each stratum of the subgroup.

^‡The P for the interaction of treatment by subgroup was derived from Wald’s test after regressing one or more indicator variables for the subgroup and for treatment group on fullness/early satiety subcore, adjusting for baseline value of fullness/early satiety subscore within each stratum of the subgroup. Bonferroni adjusted P-value for comparison of subgroup variation is 0.0002; No P-values were significant by Bonferroni-Hochberg corrected significance level, either.

^§Excludes observations with missing subgroup data.

^¶Delayed gastric emptying defined as gastric emptying scintigraphy of > 60% retention at 2 hours OR >10% retention at 4 hours, which includes the rapid emptiers.

^║Adherence defined as patient taking the treatment medication 80% of the days during the treatment period using the Drug Dispensing case-report form ((capsules dispensed – capsules returned)/3*No. days in the treatment)*100 and by the ANMS Daily-Dairy GCSI form ((capsules taken/3*No. days in diary during tx)*100.