Table 6 Inferential analysis of Drug Liking VAS Emax—esmethadone vs. ketamine and DMX.

From: The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users

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

  1. Note: Friedman’s test was used to assess overall treatment effects: p value < 0.001 for both populations.
  2. Study validity hypothesis (#1): Ho: µC – µP ≤ 15 vs. Ha: µC – µP > 15; 1-sided test (α = 0.05).
  3. Abuse potential relative to ketamine hypothesis (#2): Ho: µC – µT ≤ 0 vs. Ha: µC – µT > 0; 1-sided test (α = 0.05).
  4. Abuse potential relative to placebo hypothesis (#3): Ho: µT – µP ≥ 11 vs. Ha: µT – µP < 11; 1-sided test (α = 0.05) where P = placebo; C = positive control; and T = test drug.
  5. Exploratory hypotheses:
  6. Ho: μC2 – μP ≤ 0 vs. Ha: μC2 – μP > 0; 1-sided test (α = 0.05).
  7. Ho: μC2 – μT ≤ 0 vs. Ha: μC2 – μT > 0; 1-sided test (α = 0.05).
  8. Ho: μC1 – μC2 ≤ 0 vs. Ha: μC1 – μC2 > 0; 1-sided test (α = 0.05), where P = placebo; C1 = positive control (ketamine); C2 = exploratory comparator (DXM) and T = test drug.
  9. CI confidence interval, Emax maximum effect, VAS visual analog scale.
  10. aA paired t test was used to assess the mean difference between the 2 treatments; mean and 95% CI are presented.
  11. bThe Sign test was used to assess the median difference between the 2 treatments; median and quartiles are presented.
  12. 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.
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