Table 2.
Primary efficacy outcomes
| Study | Treatment | na | Endpoint mean pain score, LS mean | Change in pain score from baseline, LS mean (SE) | Treatment difference (pregabalin versus placebo)
|
|
|---|---|---|---|---|---|---|
| LS mean difference (95% CI) | P-value | |||||
| DPN | ||||||
| 1008-01410 | Placebo | 82 | 5.55 | −1.16 (0.23) | – | – |
| 150 mg/d | 79 | 5.11 | −1.60 (0.24) | −0.44 (−1.08 to 0.20) | 0.1763 | |
| 600 mg/d | 82 | 4.29 | −2.42 (0.23) | −1.26 (−1.89 to −0.64) | <0.0001 | |
| 1008-02911 | Placebo | 97 | 5.06 | −1.35 (0.21) | – | – |
| 75 mg/d | 77 | 4.91 | −1.50 (0.24) | −0.15 (−0.76 to 0.46) | 0.6267 | |
| 300 mg/d | 81 | 3.80 | −2.61 (0.23) | −1.26 (−1.86 to −0.65) | <0.0001 | |
| 600 mg/d | 81 | 3.60 | −2.81 (0.23) | −1.45 (−2.06 to −0.85) | <0.0001 | |
| 1008-04012,b,c | Placebo | 80 | 4.60 | −1.93 (0.27) | – | – |
| 600 mg/d | 86 | 3.96 | −2.57 (0.26) | −0.64 (−1.37 to 0.08) | 0.0822 | |
| Amit 75 mg/d | 87 | 3.67 | −2.86 (0.25) | −0.93 (−1.65 to −0.22) | 0.0110 | |
| 1008-13116 | Placebo | 69 | 5.46 | −0.88 (0.28) | – | – |
| 300 mg/d | 75 | 3.99 | −2.35 (0.26) | −1.47 (−2.19 to −0.75) | <0.0001 | |
| 1008-14917 | Placebo | 93 | 4.66 | −1.77 (0.26) | – | – |
| 150 mg/d | 96 | 4.33 | −2.10 (0.26) | −0.33 (−0.94 to 0.28) | 0.2849 | |
| 300 mg/d | 96 | 4.48 | −1.95 (0.26) | −0.17 (−0.79 to 0.43) | 0.5580 | |
| 300/600 mg/dd | 98 | 3.69 | −2.74 (0.25) | −0.97 (−1.58 to −0.36) | 0.0018 | |
| 1008-155 | Placebo | 46 | 4.86 | −1.78 (0.37) | – | – |
| (DPN patients)14 | 600 mg/d | 94 | 3.55 | −3.09 (0.27) | −1.31 (−2.16 to −0.46) | 0.0028 |
| 150–600 mg/d | 103 | 3.73 | −2.91 (0.26) | −1.13 (−1.97 to −0.29) | 0.0088 | |
| A0081030c,e | Placebo | 134 | 3.85 | −2.54 (0.19)e | – | – |
| 150–600 mg/d | 267 | 3.54 | −2.85 (0.14) | −0.30 (−0.74 to 0.13) | 0.1700 | |
| A008106020 | Placebo | 83 | 4.82 | −1.62 (0.25) | – | – |
| 600 mg/d | 80 | 3.54 | −2.90 (0.26) | −1.28 (−1.96 to −0.60) | 0.0003 | |
| A0081071c,e | Placebo | 149 | 4.16 | −2.32 (0.20)e | – | – |
| 300 mg/d | 151 | 3.97 | −2.51 (0.20) | −0.19 (−0.71 to 0.33) | 0.4744 | |
| 600 mg/d | 148 | 3.84 | −2.64 (0.20) | −0.32 (−0.85 to 0.20) | 0.4530 | |
| A0081081 | Placebo | 70 | 3.89 | −2.32 (0.25)e | – | – |
| (DPN patients)21,c,e | 150–600 mg/d | 143 | 3.50 | −2.71 (0.20) | −0.39 (−0.92 to 0.14) | 0.1523 |
| A008116322 | Placebo | 135 | 4.83 | −1.20 (0.21) | – | – |
| 300 mg/d | 134 | 4.20 | −1.82 (0.21) | −0.63 (−1.09 to −0.17) | 0.0075 | |
| 600 mg/d | 45 | 4.08 | −1.94 (0.32) | −0.74 (−1.39 to −0.09) | 0.0254 | |
| PHN | ||||||
| 1008-03012,c | Placebo | 87 | 5.59 | −0.97 (0.21) | – | – |
| 75 mg/d | 83 | 5.46 | −1.11 (0.21) | −0.14 (−0.71 to 0.43) | 0.6361 | |
| 150 mg/d | 82 | 5.52 | −1.05 (0.22) | −0.07 (−0.64 to 0.50) | 0.7999 | |
| 1008-04513 | Placebo | 81 | 6.33 | −0.52 (0.22) | – | – |
| 150 mg/d | 81 | 5.14 | −1.71 (0.22) | −1.20 (−1.81 to −0.58) | 0.0002 | |
| 300 mg/d | 76 | 4.76 | −2.09 (0.23) | −1.57 (−2.20 to −0.95) | <0.0001 | |
| 1008-12715 | Placebo | 84 | 5.29 | −1.06 (0.24) | – | – |
| 300/600 mg/dd | 88 | 3.60 | −2.75 (0.24) | −1.69 (−2.33 to −1.05) | 0.0001 | |
| 1008-19618 | Placebo | 93 | 6.14 | −0.53 (0.23) | – | – |
| 150 mg/d | 87 | 5.26 | −1.41 (0.24) | −0.88 (−1.53 to −0.23) | 0.0077 | |
| 300 mg/d | 98 | 5.07 | −1.60 (0.23) | −1.07 (−1.70 to −0.45) | 0.0008 | |
| 300/600 mg/dd | 88 | 4.35 | −2.32 (0.24) | −1.79 (−2.43 to −1.15) | 0.0001 | |
| 1008-155 | Placebo | 16 | 5.08 | −1.86 (0.71) | – | – |
| (PHN patients)14,c | 600 mg/d | 34 | 3.64 | −3.31 (0.53) | −1.45 (−2.95 to 0.06) | 0.0601 |
| 150–600 mg/d | 36 | 3.89 | −3.06 (0.49) | −1.20 (−2.69 to 0.30) | 0.1147 | |
| A008100419 | Placebo | 83 | 4.86 | −1.60 (0.21) | – | – |
| 300 mg/d | 81 | 3.86 | −2.60 (0.21) | −1.00 (−1.55 to −0.45) | 0.0004 | |
| 150–600 mg/d | 90 | 3.50 | −2.96 (0.20) | −1.36 (−1.90 to −0.83) | <0.0001 | |
| A0081081 | Placebo | 32 | 4.94 | −1.65 (0.42) | – | – |
| (PHN patients)21 | 150–600 mg/d | 60 | 3.67 | −2.93 (0.36) | −1.28 (−2.15 to −0.41) | 0.0045 |
Notes: Data for each trial are for last observation carried forward;
a
number of patients in the intent-to-treat population;
b
study 1008-040 included an active comparator arm of amitriptyline at 75 mg/day;
c
negative studies were those in which there was no significant difference at endpoint between pregabalin and placebo;
d
patients received 300 mg/day if creatinine clearance was >30 but ≤60 mL/min, and 600 mg/day if creatinine clearance was higher than 60 mL/min;
e
designated as high placebo-response studies.
Abbreviations: Amit, amitriptyline; CI, confidence interval; DPN, diabetic peripheral neuropathy; LS, least squares; PHN, postherpetic neuralgia; SE, standard error.