This work is licensed under a Table 2.
Primary and secondary efficacy outcomes; adjusted differences. Population: Full analysis set. Multiple imputation was used to address missing data. For TEWL, integrity, wound depth, and diameter, linear regression was used to estimate CIs around differences between the groups. TEWL and integrity measurements were log-transformed before analysis; differences are expressed as ratios of geometric means between groups (AZD4017:placebo). For the remaining variables, which did not meet assumptions for linear regression, median regression was used. For each variable, the comparison was adjusted for the variable’s baseline value (this was not available for wound diameter and depth), age, sex, and baseline HbA1c. All TEWL readings were adjusted using pre-disruption TEWL at baseline. Between-group differences were not calculated for biopsy and plasma AZD4017 because available placebo values did not vary, and all were below the detection limit.
| Variable | Observed | Estimated median* | Difference* | 90% CI | ||||
|---|---|---|---|---|---|---|---|---|
| Placebo | AZD4017 | Placebo, n = 14 | AZD4017, n = 14 | |||||
| Median (Q1, Q3) | n | Median (Q1, Q3) | n | |||||
| Primary outcome | ||||||||
| Skin 11β-HSD1 activity (% conversion/24 h): day 28 | ||||||||
| Radioassay | 12.0 (8.9, 14.5) | 13 | 12.7 (8.8, 15.6) | 14 | 11.8 | 12.8 | 1.1 | (−3.4, 5.5) |
| ELISA | 5.6 (1.0, 7.6) | 13 | 4.3 (3.1, 5.0) | 14 | 4.9 | 4.3 | −0.5 | (−3.8, 2.7) |
| Secondary outcomes | ||||||||
| Systemic 11β-HSD1 activity: day 35 | ||||||||
| Urinary (HF+alloTHF)/THE ratio | 0.89 (0.88, 1.24) | 13 | 0.10 (0.08, 0.12) | 13 | 1.00 | 0.13 | −0.87 | (−1.04, −0.69) |
| Cortisol (µg/24h) | 55.0 (47.0, 120.0) | 13 | 62.0 (52.0, 73.0) | 13 | 61.6 | 66.9 | 5.3 | (−30.2, 40.7) |
| Epidermal thickness (μm) | 57.5 (55.7, 67.3) | 13 | 66.3 (60.6, 74.4) | 12 | 61.2 | 66.8 | 5.6 | (−4.9, 16.0) |
| Skin hydration (A.U) | 40.5 (29.4, 46.0) | 12 | 45.3 (37.0, 46.5) | 12 | 38.0 | 43.7 | 5.7 | (−2.8, 14.1) |
| Sudomotor (nerve) function (μS): day 35 | ||||||||
| Left hand | 58.0 (48.0, 63.0) | 13 | 64.0 (59.0, 72.0) | 13 | 55.3 | 65.7 | 10.4 | (−1.8, 22.6) |
| Right hand | 55.0 (51.0, 60.0) | 13 | 63.0 (57.0, 69.0) | 13 | 55.6 | 60.6 | 5.0 | (−6.7, 16.8) |
| Hands | 57.5 (49.5, 61.0) | 13 | 63.5 (59.0, 70.5) | 13 | 55.8 | 63.0 | 7.3 | (−4.8, 19.3) |
| Left foot | 70.0 (61.0, 76.0) | 13 | 80.0 (64.0, 82.0) | 75.5 | 68.5 | −7.0 | (−18.4, 4.3) | |
| Right foot | 65.0 (63.0, 75.0) | 13 | 80.0 (68.0, 82.0) | 13 | 73.0 | 68.9 | −4.1 | (−13.2, 5.1) |
| Feet | 68.5 (62.0, 75.0) | 13 | 80.0 (66.0, 82.5) | 13 | 73.8 | 69.3 | −4.5 | (−14.5, 5.4) |
| Overall | 59.8 (53.8, 68.0) | 13 | 70.8 (64.5, 73.0) | 13 | 65.0 | 63.7 | −1.3 | (−9.2, 6.6) |
| AZD4017 (nmol/L) | ||||||||
| Biopsy: day 28 | <5 (<5, <5) | 13 | 1570 (876, 2440) | 14 | ||||
| Plasma: day 35 | <5 (<5, <5) | 7 | 6490 (2960, 9040) | 12 | ||||
| Wound healing (mm) after day 0 biopsies | ||||||||
| Diameter: day 2 | 1.49 (0.72) | 14 | 0.98 (0.70) | 14 | 1.51 | 0.98 | −0.52 | (−0.95, −0.10) |
| Depth: day 7 | 0.60 (0.23) | 14 | 0.59 (0.16) | 14 | 0.60 | 0.59 | −0.01 | (−0.15, 0.13) |
| Wound healing after day 28 biopsies | ||||||||
| Diameter: day 30 | 1.44 (0.70) | 11 | 0.65 (0.49) | 12 | 1.35 | 0.70 | −0.65 | (−1.15, 0.16) |
| Depth: day 35 | 0.60 (0.17) | 13 | 0.54 (0.21) | 12 | 0.59 | 0.56 | −0.03 | (−0.16, 0.09) |
| Epidermal barrier TEWL (g/h/m2): day 35 | 1.9 (0.4); 7.0 | 13 | 2.2 (0.5); 8.9 | 12 | 6.9 | 9.2 | 1.33 | (0.97, 1.82) |
| Epidermal integrity (tape strips): day 28 | 3.6 (0.6); 37.9 | 13 | 4.0 (0.4); 55.6 | 14 | 39.0 | 55.8 | 1.43 | (1.07, 1.91) |
| Epidermal barrier recovery TEWL (g/h/m2) after day 0 disruption | ||||||||
| Hour 3 | 3.6 (0.3); 34.9 | 14 | 3.4 (0.2); 30.8 | 12 | 35.1 | 32.0 | 0.91 | (0.76, 1.09) |
| Hour 48 | 3.0 (0.3); 19.8 | 14 | 3.1 (0.4); 21.3 | 11 | 20.4 | 20.6 | 1.01 | (0.79, 1.28) |
| Hour 168 | 2.6 (0.3); 13.5 | 13 | 2.8 (0.7); 16.1 | 13 | 14.1 | 15.6 | 1.11 | (0.76, 1.62) |
| Epidermal barrier recovery TEWL (g/h/m2) after day 28 disruption | ||||||||
| Hour 3 | 3.2 (0.5); 23.8 | 13 | 3.4 (0.3); 29.8 | 14 | 23.0 | 30.7 | 1.33 | (0.99, 1.79) |
| Hour 48 | 2.7 (0.4); 14.4 | 13 | 2.9 (0.4); 18.2 | 14 | 14.6 | 18.4 | 1.26 | (0.94, 1.67) |
| Hour 168 | 2.3 (0.4); 10.0 | 13 | 2.4 (0.4); 10.8 | 12 | 10.1 | 10.8 | 1.07 | (0.79, 1.44) |
*Estimated using multiple imputation, adjusted for baseline value (if applicable), age, sex, and baseline HbA1c.