Clinical experience with desvenlafaxine in treatment of pain associated with diabetic peripheral neuropathy

Figures & data

Figure 1 Study flowchart.

Abbreviation: ITT, intent-to-treat.

Table 1 Demographics and baseline characteristics, short-term study (safety population)

Characteristic	Placebo (n=90)	Desvenlafaxine
		50 mg (n=63)	100 mg (n=87)	200 mg (n=99)	400 mg (n=69)
Age, mean ± SD (years)	59.0±8.5	61.6±8.6	60.7±9.2	59.8±9.4	61.1±10.0
Sex, n (%)
Women	25 (28)	16 (25)	20 (23)	30 (30)	17 (25)
Men	65 (72)	47 (75)	67 (77)	69 (70)	52 (75)
Race, n (%)
American Indian or Alaska Native	2 (2.22)	0	1 (1.15)	0	1 (1.45)
Asian	0	0	1 (1.15)	0	0
Black or African-American	8 (8.9)	4 (6.4)	6 (6.9)	6 (6.1)	7 (10.1)
Other	4 (4.4)	4 (6.3)	2 (2.3)	5 (5.1)	3 (4.3)
White	76 (84.4)	55 (87.3)	77 (88.5)	88 (88.9)	58 (84.1)
Weight,a mean ± SD (kg)	110.1±26.5	111.0±24.3	108.2±19.9	100.6±20.9	107.0±23.1
Duration of neuropathic pain, median (months) (range)	42.1 (5.8–250.8)	41.8 (3.2–431.5)	45.3 (5.5–196.5)	40.6 (5.3–335.1)	40.4 (5.3–199.8)
Duration of diabetes, median (years) (range)	8.2 (1.0–49.4)	6.9 (0.3–40.1)	7.8 (0.5–38.0)	8.4 (0.1–41.0)	6.6 (0.5–43.4)
Baseline NRS, mean ± SD	6.61 ±1.60	6.44±1.66	6.14±1.62	6.55±1.52	6.48±1.42

Note:

a One-way analysis of variance with treatment as factor, P=0.025.

Abbreviations: NRS, numeric rating scale; SD, standard deviation.

Figure 2 Adjusted mean change from baseline on NRS pain severity over time (ITT; MMRM).

Notes: ^aP=0.084 (Hochberg) for desvenlafaxine 50 mg and 100 mg groups versus placebo; ^bP=0.027 (Hochberg) for desvenlafaxine 400 mg versus placebo; ^cP=0.001 (Hochberg) for desvenlafaxine 200 mg versus placebo.
Abbreviations: ITT, intent-to-treat; MMRM, mixed-effects model for repeated measures; NRS, numeric rating scale.

Figure 3 Response rate on pain severity score on the NRS at week 13 (ITT).

Notes: ^aNRS response is defined as a reduction of 50% or more from baseline; ^bno significant differences from placebo for active treatment groups.
Abbreviations: ITT, intent-to-treat; NRS, numeric rating scale.

Figure 4 Proportions of patients achieving minimum thresholds of reduction in NRS score at week 13 (ITT).

Abbreviations: ITT, intent-to-treat; NRS, numeric rating scale.

Table 2 Secondary efficacy endpoints (MMRM), short-term study (intent-to-treat population)

	Number of patients	Adjusted mean score ± SE	Adjusted mean difference from placebo (95% CI)	P-value vs placebo
PGI-C
Desvenlafaxine 50 mg	54	2.74±0.15	0.39 (0.00 to 0.78)	0.049
Desvenlafaxine 100 mg	70	2.71±0.13	0.42 (0.06 to 0.78)	0.023
Desvenlafaxine 200 mg	69	2.35±0.13	0.79 (0.42 to 1.15)	<0.001
Desvenlafaxine 400 mg	45	2.52±0.16	0.61 (0.21 to 1.01)	0.003
Placebo	76	3.13±0.13
CGI-C
Desvenlafaxine 50 mg	53	2.50±0.15	0.45 (0.07 to 0.82)	0.019
Desvenlafaxine 100 mg	71	2.63±0.13	0.32 (−0.02 to 0.67)	0.066
Desvenlafaxine 200 mg	71	2.54±0.12	0.42 (0.07 to 0.76)	0.018
Desvenlafaxine 400 mg	46	2.78±0.15	0.18 (−0.20 to 0.55)	0.364
Placebo	77	2.95±0.12
SIS
Desvenlafaxine 50 mg	54	−1.81±0.31	0.48 (−0.31 to 1.28)	0.230
Desvenlafaxine 100 mg	69	−2.11±0.27	0.78 (0.04 to 1.52)	0.039
Desvenlafaxine 200 mg	69	−2.63±0.27	1.30 (0.56 to 2.04)	<0.001
Desvenlafaxine 400 mg	44	−2.32±0.34	0.99 (0.16 to 1.83)	0.020
Placebo	76	−1.33±0.26
PGSR
Desvenlafaxine 50 mg	54	−1.08±0.13	0.25 (−0.07 to 0.58)	0.129
Desvenlafaxine 100 mg	70	−1.10±0.11	0.27 (−0.03 to 0.58)	0.078
Desvenlafaxine 200 mg	69	−0.92±0.12	0.10 (−0.21 to 0.41)	0.525
Desvenlafaxine 400 mg	45	−1.18±0.14	0.36 (0.02 to 0.71)	0.038
Placebo	76	−0.82±0.11
PGR
Desvenlafaxine 50 mg	53	−1.14±0.13	0.33 (0.00 to 0.65)	0.048
Desvenlafaxine 100 mg	71	−0.96±0.11	0.15 (−0.15 to 0.45)	0.315
Desvenlafaxine 200 mg	71	−0.86±0.11	0.05 (−0.24 to 0.35)	0.724
Desvenlafaxine 400 mg	46	−0.95±0.14	0.14 (−0.20 to 0.48)	0.415
Placebo	77	−0.81±0.11

Abbreviations: CGI-C, Clinical Global Impression of Change; CI, confidence interval; MMRM, mixed-effects model for repeated measures; PGI-C, Patient Global Impression of Change; PGSR, Patient Global Symptom Rating; PGR, Physician Global Rating; SIS, Sleep Interference Scale; vs, versus.

Table 3 Treatment-emergent adverse events in ≥5% and twice that of placebo for patients in any treatment group, short-term study (safety population)

Adverse event	Placebo (n=90)	Desvenlafaxine
		50 mg (n=63)	100 mg (n=87)	200 mg (n=99)	400 mg (n=69)
Any adverse event, n (%)	68 (75.6)	47 (74.6)	65 (74.7)	82 (82.8)	63 (91.3)
Constipation	0	3 (4.8)	4 (4.6)	6 (6.1)	6 (8.7)
Decreased appetite	2 (2.2)	2 (3.2)	2 (2.3)	5 (5.1)	3 (4.3)
Dizziness	7 (7.8)	1 (1.6)	7 (8.0)	18 (18.2)	18 (26.1)
Dry mouth	2 (2.2)	2 (3.2)	4 (4.6)	6 (6.1)	9 (13.0)
Fatigue	4 (4.4)	4 (6.3)	6 (6.9)	8 (8.1)	8 (11.6)
Insomnia	1 (1.1)	3 (4.8)	1 (1.1)	4 (4.0)	5 (7.2)
Lethargy	0	1 (1.6)	2 (2.3)	5 (5.1)	2 (2.9)
Muscle spasms	4 (4.4)	6 (9.5)	4 (4.6)	4 (4.0)	3 (4.3)
Pain in extremity	0	4 (6.3)	1 (1.1)	1 (1.0)	1 (1.4)
Nasopharyngitis	1 (1.1)	2 (3.2)	6 (6.9)	5 (5.1)	3 (4.3)
Nausea	2 (2.2)	9 (14.3)	11 (12.6)	27 (27.3)	12 (17.4)
Somnolence	1 (1.1)	1 (1.6)	6 (6.9)	4 (4.0)	5 (7.2)
Vomiting	2 (2.2)	3 (4.8)	3 (3.4)	10 (10.1)	2 (2.9)
Weight decreased	0	0	0	1 (1.0)	4 (5.8)

Table 4 Selected vital signs and laboratory values at week 13 (LOCF), short-term study (safety population)

	Baseline mean	Week 13 adjusted mean change from baseline ± SE	P-value vs placebo
Alkaline phosphatase (mU/mL)
Desvenlafaxine 50 mg	68.1	1.8±1.7	0.731
Desvenlafaxine 100 mg	74.4	5.0±1.4	0.218
Desvenlafaxine 200 mg	73.3	6.0±1.5	0.087
Desvenlafaxine 400 mg	84.2	10.5±1.9	<0.001
Placebo	75.4	2.5±1.4
Total cholesterol† (mmol/L)
Desvenlafaxine 50 mg	4.461	−0.050±0.101	0.481
Desvenlafaxine 100 mg	4.271	0.087±0.088	0.063
Desvenlafaxine 200 mg	4.372	0.153±0.091	0.019
Desvenlafaxine 400 mg	4.420	0.225±0.114	0.011
Placebo	4.303	−0.144±0.087
HDL cholesterol† (mmol/L)
Desvenlafaxine 50 mg	1.259	−0.018±0.024	0.257
Desvenlafaxine 100 mg	1.185	0.017±0.021	0.016
Desvenlafaxine 200 mg	1.244	0.026±0.021	0.007
Desvenlafaxine 400 mg	1.292	0.084±0.027	<0.001
Placebo	1.222	−0.054±0.020
Weight (kg)
Desvenlafaxine 50 mg	110.03	−1.03±0.47	0.144
Desvenlafaxine 100 mg	110.10	−1.26±0.41	0.047
Desvenlafaxine 200 mg	102.78	−1.53±0.42	0.016
Desvenlafaxine 400 mg	105.03	−3.28±0.53	<0.001
Placebo	111.62	−0.13±0.39
Heart rate,* (bpm)
Desvenlafaxine 50 mg	68.39	1.42±1.24	0.374
Desvenlafaxine 100 mg	68.02	2.14±1.10	0.157
Desvenlafaxine 200 mg	69.70	3.99±1.15	0.011
Desvenlafaxine 400 mg	70.83	5.62±1.41	0.002
Placebo	68.63	−0.04±1.07

Notes:

* 12-lead ECG

† fasting.

Abbreviations: bpm, beats per minute; ECG, electrocardiogram; HDL, high-density lipoprotein; LOCF, last observation carried forward; vs, versus.