Table 3.
Clinical research unit and outpatient outcomes by treatment regimen
| Parameter | Endpoint type | Mean value (SD) (N = 17) | Avexitide 30 twice daily (N = 17) | Avexitide 60 once daily (N = 17) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Placebo (N = 17) | Avexitide 30 twice daily (N = 17) | Avexitide 60 once daily (N = 17) | Placebo-corrected valuea (SE) | 95% CI | P | Placebo-corrected valuea (SE) | 95% CI | P | ||
| Outcomes during MMTT provocation in the Clinical Research Unit | ||||||||||
| Glucose | ||||||||||
| Fasting (mg/dL) | — | 83.8 (5.3) | 87.5 (6.0) | 84.6 (4.2) | 3.8 (1.1) | 1.52, 5.99 | .003 | 0.85 (1.05) | –1.38, 3.09 | .428 |
| Peak (mg/dL) | — | 211.8 (38.5) | 218.2 (45.2) | 224.5 (47.3) | 6.3 (4.8) | –3.85, 16.49 | .205 | 11.87 (4.77) | 1.70, 22.05 | .025 |
| Nadir (mg/dL) | Primary | 47.1 (12.7) | 57.1 (16.5) | 59.2 (16.1) | 10.1 (2.5) | 4.77, 15.44 | .001 | 12.19 (2.50) | 6.85, 17.52 | .000 |
| AUC(0–180) (h × mg/dL) | — | 286.9 (70.1) | 320.0 (89.5) | 338.1 (80.7) | 33.2 (10.9) | 10.10, 56.36 | .008 | 50.09 (10.85) | 26.96, 73.23 | .000 |
| AUC(peak:nadir) (h × mg/dL) | — | 161.8 (56.5) | 192.3 (91.9) | 204.6 (86.3) | 30.4 (12.3) | 4.18, 56.7 | .026 | 41.57 (12.34) | 15.27, 67.86 | .004 |
| Insulin | ||||||||||
| Fasting (μIU/mL) | — | 4.5 (2.4) | 4.5 (2.7) | 4.1 (2.6) | 0.03 (0.35) | –0.71, 0.78 | .922 | –0.43 (0.35) | –1.18, 0.32 | .238 |
| Peak (μIU/mL) | Secondary | 454.5 (240.1) | 349.5 (156.9) | 357.2 (190.9) | –104.5 (43.2) | –196.7, –12.38 | .029 | –96.29 (43.24) | –188.5, –4.14 | .042 |
| GLP-1 | ||||||||||
| Fasting (pg/mL) | — | 12.5 (6.0) | 12.7 (3.4) | 12.7 (4.6) | 0.31 (1.23) | –2.31, 2.94 | .803 | 0.28 (1.23) | –2.35, 2.91 | .824 |
| Peak (pg/mL) | — | 326.5 (149.4) | 413.3 (193.6) | 397.1 (150.2) | 87.1 (27.6) | 28.40, 145.8 | .006 | 71.20 (27.55) | 12.48, 129.9 | .021 |
| AUC(0–180) (h×mg/dL) | — | 277.0 (117.0) | 330.8 (140.5) | 351.1 (127.5) | 53.8 (18.0) | 15.48, 92.07 | .009 | 74.74 (17.97) | 36.44, 113.0 | .001 |
| Glucagon | ||||||||||
| Fasting (pg/mL) | — | 156.3 (0) | 156.3 (0) | 156.8 (2.2) | 0.00 (0.37) | –0.79, 0.79 | 1.000 | 0.56 (0.37) | –0.23, 1.34 | .153 |
| Peak (pg/mL) | — | 178.5 (33.3) | 196.7 (49.8) | 182.9 (35.9) | 18.3 (8.4) | 0.29, 36.20 | .047 | 4.53 (8.42) | –13.43, 22.48 | .599 |
| AUC(0–180) (h × mg/dL) | — | 423.5 (108.2) | 466.7 (131.2) | 484.1 (96.7) | 43.6 (27.5) | –14.88, 102.15 | .133 | 61.21 (27.45) | 2.69, 119.7 | .042 |
| Outcomes captured by SMBG/eDiary in the outpatient setting | ||||||||||
| Rateb of Level 1c hypoglycemia | Expl. | 4.03 (3.10) | 2.81 (2.13) | 1.56 (1.27) | –1.24 (0.64) | –2.62, 0.13 | .072 | –2.51 (0.64) | –3.88, –1.14 | .001 |
| Rate of Level 2d hypoglycemia | Expl. | 2.01 (1.69) | 1.21 (1.65) | 0.81 (0.88) | –0.77 (0.34) | –1.49, –0.04 | .040 | –1.17 (0.34) | –1.90, –0.44 | .004 |
| Rate of Level 3e hypoglycemia | Expl. | 1.96 (1.94) | 1.50 (2.36) | 0.86 (1.16) | –0.49 (0.39) | –1.32, 0.34 | .224 | –1.09 (0.39) | –1.92, –0.26 | .014 |
| Outcomes captured by CGM in the outpatient setting | ||||||||||
| % Timef <54 mg/dL 8 am-12 am | Expl. | 1.97 (1.64) | 0.99 (1.12) | 1.49 (1.70) | –0.93 (0.34) | –1.65, –0.22 | .014 | –0.44 (0.34) | –1.15, 0.28 | .209 |
| % Time <54 mg/dL 12 am-8 am | — | 2.16 (2.54|) | 2.06 (2.36) | 2.95 (3.50) | –0.10 (0.79) | –1.79, 1.59 | .902 | 0.75 (0.79) | –0.94, 2.44 | .359 |
| % Time >250 mg/dL 24 hours | Expl. | 0.62 (0.82) | 0.99 (1.34) | 0.85 (0.98) | 0.34 (0.16) | 0.001, 0.680 | .049 | 0.13 (0.16) | –0.21, 0.47 | .416 |
| No. eventsg <54 mg/dL 8 am-12 am | Expl. | 4.92 (4.08) | 2.82 (3.00) | 3.46 (2.48) | –2.00 (0.67) | –3.43, –0.58 | .009 | –1.39 (0.67) | –2.82, 0.03 | .055 |
| No. events <54 mg/dL 12 am-8 am | — | 2.12 (2.30) | 2.34 (3.03) | 3.56 (4.18) | 0.23 (0.77) | –1.40, 1.86 | .768 | 1.38 (0.77) | –0.25, 3.01 | .092 |
Mean values represent pooled data by treatment. Two-sided P-value versus placebo are shown (Fisher’s exact test). P ≤ .05 shown in bold font. AUC0–180 denotes area under the concentration-time curve from 0 to 180 minutes; avexitide 30 twice daily, avexitide 30 mg dose every 12 hours; avexitide 60 once daily, avexitide 60 mg dose once each morning.
Abbreviations: CI, confidence interval; Expl., exploratory endpoint;
a Placebo-corrected values represent the least squared mean difference between the placebo and avexitide result.
b Rates are expressed as number of distinct episodes divided by number of days for a given treatment period, then normalized to duration of 14 days if the treatment period was not exactly 14 days.
c Level 1 hypoglycemia is defined as SMBG < 70 mg/dL (3.9 mmol/L) and glucose ≥54 mg/dL (3.0 mmol/L).
d Level 2 hypoglycemia is defined as SMBG < 54 mg/dL (3.0 mmol/L).
e Level 3 hypoglycemia is defined as severe hypoglycemia; a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. This applies regardless of whether a patient actually receives external assistance.
f Percent time is expressed as the percentage of CGM values that are above or below the stated glycemic threshold during each treatment period.
g Number of events is defined as the number of occurrences with CGM glucose measurements <54 mg/dL sustained for at least 15 minutes during the specified time period (8 am-12 am or 12 am-8 am) during each treatment period, normalized to 14 days.