Table 3.
Respiratory Parameters from Polysomnography
| Parameter/Arm | Baseline | Treatment | Placebo-adjusted Change from Baseline |
|---|---|---|---|
| AHI4 events/h | |||
| Placebo | 20.1 (11.9–25.9) | 16.3 (11.1–28.9) | – |
| Ato75 | 19.0 (11.8–28.8) | 11.8 (5.5–21.5) | −5.19 (−8.6 to −1.8)** |
| AD109 2.5/75 mg | 20.5 (12.3–27.2) | 10.8 (5.6–18.5) | −7.16 (−11.0 to −3.3)*** |
| AD109 5/75 mg | 19.4 (13.7–26.4) | 9.5 (6.1–19.3) | −7.20 (−10.97 to −3.4)*** |
| AHI4 supine events/h | |||
| Placebo | 32.7 (19.0–44.9) | 28.4 (17.3–48.0) | – |
| Ato75 | 29.3 (18.3–45.7) | 17.8 (6.6–38.8) | −7.06 (−12.47 to −1.66)* |
| AD109 2.5/75 mg | 29.2 (17.5–46.9) | 18.3 (7.7–26.5) | −8.58 (−14.71 to −2.45)** |
| AD109 5/75 mg | 39.7 (21.6–54.6) | 17.8 (9.5–43.6) | −10.62 (−16.70 to −4.54)*** |
| AHI4 lateral events/h | |||
| Placebo | 10.5 (5.1–10.1) | 9.2 (4.0–16.6) | – |
| Ato75 | 11.1 (3.8–18.4 | 6.0 (2.1–16.2) | −4.31 (−8.97 to 0.35) |
| AD109 2.5/75 mg | 12.4 (4.3–24.6) | 5.7 (3.7–13.7) | −5.89 (−11.02 to −0.76)* |
| AD109 5/75 mg | 14.7 (7.4–25.9) | 7.5 (4.7–14.0) | −6.42 (−11.55 to −1.29)* |
| AHI4 NREM sleep events/h | |||
| Placebo | 19.3 (9.4–27.7) | 16.7 (9.2–27.3) | – |
| Ato75 | 18.4 (9.4–28.6) | 11.4 (4.4–19.4) | −4.22 (−7.81 to −0.63)* |
| AD109 2.5/75 mg | 16.0 (9.6–24.7) | 10.1 (3.5–16.4) | −5.38 (−9.41 to −1.34)** |
| AD109 5/75 mg | 19.0 (10.1–30.7) | 8.3 (5.9–19.5) | −6.45 (−10.44 to −2.46)** |
| AHI4 REM sleep events/h† | |||
| Placebo | 20.9 (9.3–33.9) | 20.3 (6.1–36.1) | – |
| Ato75 | 28.1 (15.7–21.6) | 18.5 (9.1–26.8) | −5.77 (−11.66 to 0.71) |
| AD109 2.5/75 mg | 30.2 (18.1–50.7) | 18.2 (7.6–43.5) | −5.67 (−12.74 to 1.41) |
| AD109 5/75 mg | 22.6 (13.0–34.4) | 13.8 (6.6–31.8) | −3.34 (−10.39 to 3.72) |
| AHI3a events/h | |||
| Placebo | 35.5 (25.6–41.0) | 31.5 (23.0–41.1) | – |
| Ato75 | 33.4 (25.0–45.7) | 26.1 (14.5–42.1) | −3.71 (−8.19 to 0.76) |
| AD109 2.5/75 mg | 37.6 (30.0–47.4) | 28.3 (18.3–39.8) | −7.03 (−12.08 to -1.98)** |
| AD109 5/75 mg | 35.9 (25.5–48.9) | 22.1 (15.9–38.4) | −7.11 (−12.08 to -2.14)** |
| Log10(HB + 1) | |||
| Placebo | 1.51 (1.25–1.75) | 1.48 (1.20–1.73) | – |
| Ato75 | 1.54 (1.36–1.70) | 1.30 (0.95–1.63) | −0.23 (−0.36 to −0.09)** |
| AD109 2.5/75 mg | 1.46 (1.24–1.78) | 1.36 (1.01–1.58) | −0.19 (−0.34 to −0.04)* |
| AD109 5/75 mg | 1.49 (1.34–1.79) | 1.24 (0.97–1.51) | −0.23 (−0.38 to −0.09)*** |
| HB geometric means (95% CI), %min/h | |||
| Placebo | 31.1 (25.8–38.2) | 30.1 (25.0–38.3) | – |
| Ato75 | 31.9 (27.2–40.5) | 18.0 (12.4–26.0) | – |
| AD109 2.5/75 mg | 31.0 (25.1–41.2) | 19.1 (11.3–28.2) | – |
| AD109 5/75 mg | 32.4 (25.6–41.5) | 18.0 (12.0–26.1) | – |
| ODI4 events/h | |||
| Placebo | 26.3 (17.7–35.0) | 23.4 (14.8–35.3) | – |
| Ato75 | 25.8 (17.7–32.8) | 19.0 (11.0–29.6) | −4.82 (−8.16 to −1.49)** |
| AD109 2.5/75 mg | 29.1 (21.9–34.0) | 19.0 (8.3–29.8) | −5.63 (−9.38 to −1.89)** |
| AD109 5/75 mg | 25.5 (18.4–37.5) | 16.9 (9.4–26.3) | −6.01 (−9.71 to −2.30)** |
| T90 minimum | |||
| Placebo | 11.5 (5.5–23.7) | 11.3 (5.0–21.1) | – |
| Ato75 | 14.4 (8.4–31.2) | 9.9 (1.8–24.6) | −5.56 (−12.67 to 1.56) |
| AD109 2.5/75 mg | 9.8 (4.1–25.9) | 7.2 (1.0–13.8) | −3.20 (−11.12 to 4.72) |
| AD109 5/75 mg | 10.4 (3.6–27.3) | 5.8 (1.8–17.8) | −3.68 (−11.50 to 4.15) |
| Proportion (95% CI) of participants with >50% reduction in AHI4 | |||
| Placebo | – | 16.6 (8.4–28.3) | Odds ratio vs placebo |
| Ato75 | – | 39.4 (25.8–54.3) | 3.47 (1.57–7.71)** |
| AD109 2.5/75 mg | – | 43.2 (26.3–61.4) | 4.00 (1.68–9.51)** |
| AD109 5/75 mg | – | 44.3 (27.6–62.0) | 4.23 (1.80–9.97)** |
Definition of abbreviations: Ato75 = atomoxetine 75 mg; AHI4 = apnea–hypopnea index (⩾4% desaturation criterion for hypopneas); AHI3a = apnea–hypopnea index (⩾3% desaturation or arousal definition for hypopneas); CI = confidence interval; HB = hypoxic burden; Log10(HB + 1) = logarithm base 10 of hypoxic burden + 1; NREM = non-REM; ODI4 = oxygen desaturation index using ⩾4% desaturation criterion; T90 = time spent during sleep with oxygen saturation <90%.
Baseline and treatment data are shown as median (IQR) unless otherwise specified. Placebo-adjusted change from baseline data are shown as least-square mean (LSmean) (95% CI).
P < 0.05, **P < 0.01, ***P < 0.001 vs. placebo.
Sleep studies with ⩾10 minutes of REM sleep were included in this analysis.