Table 6.

Inferential analysis of Drug Liking VAS E_max—esmethadone vs. ketamine and DMX.

Study validity
Ketamine 0.5 mg/kg – Placebo	49.0	(27.0, 50.0)b	<0.001
Drug Liking VAS Emax relative to ketamine
Ketamine 0.5 mg/kg – Esmethadone 25 mg	48.0	(27.0, 50.0)b	<0.001
Ketamine 0.5 mg/kg – Esmethadone 75 mg	40.0	(25.0, 50.0)b	<0.001
Ketamine 0.5 mg/kg – Esmethadone 150 mg	34.0	(18.0, 49.0)b	<0.001
Drug Liking VAS Emax relative to placebo
Esmethadone 25 mg – Placebo	0.0	(0.0, 0.0)b	<0.001
Esmethadone 75 mg – Placebo	0.0	(0.0, 3.0)b	<0.001
Esmethadone 150 mg – Placebo	0.0	(0.0, 14.0)b	0.003
Exploratory comparisons
DXM 300 mg – Placebo	8.0	(0.0, 35.0)b	0.39
DXM 300 mg – Esmethadone 25 mg	10.0	(0.0, 34.0)b	<0.001
DXM 300 mg – Esmethadone 75 mg	13.5	(8.6, ∞)a	<0.001
DXM 300 mg – Esmethadone 150 mg	9.2	(4.1, ∞)a	0.002
Ketamine 0.5 mg/kg – DXM 300 mg	21.6	(17.1, ∞)a	<0.001

Note: Friedman’s test was used to assess overall treatment effects: p value < 0.001 for both populations.

Study validity hypothesis (#1): H_o: µ_C – µ_P ≤ 15 vs. H_a: µ_C – µ_P > 15; 1-sided test (α = 0.05).

Abuse potential relative to ketamine hypothesis (#2): H_o: µ_C – µ_T ≤ 0 vs. H_a: µ_C – µ_T > 0; 1-sided test (α = 0.05).

Abuse potential relative to placebo hypothesis (#3): H_o: µ_T – µ_P ≥ 11 vs. H_a: µ_T – µ_P < 11; 1-sided test (α = 0.05) where P = placebo; C = positive control; and T = test drug.

Exploratory hypotheses:

H_o: μ_C2 – μ_P ≤ 0 vs. H_a: μ_C2 – μ_P > 0; 1-sided test (α = 0.05).

H_o: μ_C2 – μ_T ≤ 0 vs. H_a: μ_C2 – μ_T > 0; 1-sided test (α = 0.05).

H_o: μ_C1 – μ_C2 ≤ 0 vs. H_a: μ_C1 – μ_C2 > 0; 1-sided test (α = 0.05), where P = placebo; C₁ = positive control (ketamine); C₂ = exploratory comparator (DXM) and T = test drug.

CI confidence interval, E_max maximum effect, VAS visual analog scale.

^aA paired t test was used to assess the mean difference between the 2 treatments; mean and 95% CI are presented.

^bThe Sign test was used to assess the median difference between the 2 treatments; median and quartiles are presented.

Bolded p-values are statistically significant. A statistically significant p-value for the comparison of esmethadone vs. placebo indicates that esmethadone at that dose level has a response profile equivalent to placebo. The nonsignificant p-value reported for DXM vs. placebo indicates that DXM at that dose level lacks placebo equivalency.