Extended Data Table 1.
Demographic Characteristics of Volunteers in SAD and MAD Studies and Baseline-to-End (Day 1 to Day 15) Treatment Profile of MAD Cohorts
| Demographic and clinical characteristics of the single ascending dose (SAD) participants at baseline | ||||||
| SAD GROUP | Number of patients | 17 | Race or ethnic group | Number (%) | Average body weight/weight range (kg) | 74 /58-102 |
| Average patient age (years) | 36 | White | 15 (88%) | Average Body Mass Index / range | 25 / 20-30 | |
| Age range (years) | 18-58 | Asian | 1 (6%) | BMI Distribution | Number (%) | |
| Number (percent) of female patients | 8 (47%) | Black | 0 | <20 | 0 (0%) | |
| Other | 1 (6%) | ≥20 - <25 | 7 (41%) | |||
| Number (percent) of male patients | 9 (53%) | Hispanic or Latino | 4 (24%) | ≥25 - ≤30 | 10 (59%) | |
| Doses by Cohort | mg/dose | Doses (mg/dose/Kg) by Cohort | Average (range) | |||
| SAD 1 | 200 | SAD 1 | 2.8 (2.7 - 3.3) | |||
| SAD 2 | 400 | SAD 2 | 5.3 (3.3 - 6.9) | |||
| SAD 3 | 800 | SAD 3 | 11.4 (8.3 - 13.9) | |||
| Demographic and clinical characteristics of the multiple ascending dose (MAD) participants at baseline | ||||||
| MAD GROUP | Number of patients | 24 | Race or Ethnic Group | Number (%) | Average body weight / weight range (kg) | 93 / 77-109 |
| Average patient age (years) | 35 | White | 13 (57%) | Average body mass index | 31 / 28-34 | |
| Age range (years) | 26-55 | Asian | 7 (30%) | BMI distribution | Number (%) | |
| Number (percentage) of female patients | 5 (22%) | Black | 1 (4%) | ≥28 - <30 | 10 (43%) | |
| Other | 2 (9%) | ≥30 - ≤35 | 13 (57%) | |||
| Number (percent) of male patients | 18 (78%) | Hispanic or Latino | 4 (17%) | >35 | 0 | |
| Doses by cohort | mg/dose | Doses (mg/dose/Kg) by Cohort | Average (range) | |||
| MAD 1 | 100 | MAD 1 | 1.0 (0.9 - 1.2) | |||
| MAD 2 | 150 | MAD 2 | 1.7 (1.4 - 1.9) | |||
| MAD 3 | 200 | MAD 3 | 2.1 (1.9- 2.2) | |||
| Characteristics of MAD participants in each cohort at the baseline (day 1) and at the end of the treatment (day 15) | ||||||||||||
| PLACEBO | ||||||||||||
| Weight (kg) | BMI | Fasting Glucose (g/L) | Fasting Insulin (mU/L) | HOMA-IR | Fructasamine (umol/L) | |||||||
| day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | |
| Placebos | p = 0,21 (n = 3) | p = 0,24 (n = 3) | p = 0,17 (n = 5) | p = 0,19 (n = 5) | p = 0,13 (n = 5) | p = 0,48 (n = 5) | ||||||
| P1 | 108.3 | ND | 33.1 | ND | 0.92 | 0.86 | 9 | 7 | 2.0 | 1.5 | < 30 | 324 |
| P2 | 82.4 | ND | 28.1 | ND | 0.86 | 0.83 | 8 | 9 | 1.7 | 1.8 | 295 | 303 |
| P3 | 83.7 | 81.7 | 30.8 | 30.1 | 0.85 | 0.76 | 13 | 11 | 2.7 | 2.1 | 256 | 242 |
| P4 | 103.6 | 103.5 | 34.4 | 34.4 | 0.74 | 0.77 | 7 | 5 | 1.3 | 1.0 | 263 | 198 |
| P5 | 89.1 | 88.2 | 29.6 | 29.3 | 0.74 | 0.72 | 6 | 6 | 1.1 | 1.1 | 215 | 238 |
| ACTIVE | ||||||||||||
| Weight (kg) | BMI | Fasting Glucose (g/L) | Fasting Insulin (mU/L) | HOMA-IR | Fructasamine (umol/L) | |||||||
| MAD Coh.1 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 |
| 200 mg/day | p = ND (n = 1) | p = ND (n = 1) | p = 0,01 (n = 5) | p = 0,10 (n = 5) | p = 0,05 (n = 5) | p = 0,22 (n = 5) | ||||||
| P6 | 97.7 | ND | 30.7 | ND | 1.24 | 1.01 | 18 | 20 | 5.5 | 5.0 | < 30 | 356 |
| P7 | 101.5 | ND | 29.2 | ND | 0.92 | 0.76 | 4 | 4 | 0.9 | 0.8 | < 30 | 326 |
| P8 | 100.4 | ND | 32.5 | ND | 0.94 | 0.85 | 14 | 2 | 3.2 | 0.4 | 323 | 300 |
| P9 | 90.3 | ND | 32.9 | ND | 0.90 | 0.83 | 25 | 14 | 5.6 | 2.9 | 286 | 274 |
| P10 | 104.1 | 101 | 33.8 | 32.8 | 0.94 | 0.81 | 21 | 7 | 4.9 | 1.4 | 212 | ND |
| MAD Coh.2 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 |
| 300 mg/day | p = 0,01 (n = 6) | p = 0,02 (n = 6) | p = 0,47 (n = 6) | p = 0,58 (n = 6) | p = 0,65 (n = 6) | p = 0,40 (n = 6) | ||||||
| P11 | 81.1 | 78.9 | 28.3 | 27.5 | 0.81 | 0.81 | 5 | 6 | 1.0 | 1.2 | 313 | 322 |
| P12 | 95.7 | 95.1 | 29.4 | 29.2 | 0.85 | 0.83 | 2 | 14 | 0.4 | 2.9 | 292 | 264 |
| P13 | 78.1 | 76.9 | 30.3 | 29.8 | 0.92 | 0.86 | 13 | 11 | 3.0 | 2.3 | 266 | 250 |
| P14 | 77.1 | 75 | 30.4 | 29.6 | 0.85 | 0.79 | 8 | 9 | 1.7 | 1.8 | 251 | 249 |
| P15 | 83.7 | 83.7 | 29.0 | 29.0 | 0.79 | 0.83 | 6 | 6 | 1.2 | 1.2 | 312 | 326 |
| P16 | 109.1 | 107.5 | 34.3 | 33.8 | 0.77 | 0.79 | 8 | 4 | 1.5 | 0.8 | 184 | 171 |
| MAD Coh.3 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 | day 1 | day 15 |
| 400 mg/day | p = 0,01 (n = 6) | p = 0,007 (n = 6) | p = 0,31 (n = 6) | p = 0,04 (n = 6) | p = 0,03 (n = 6) | p = 0,004 (n = 6) | ||||||
| P17 | 92.2 | 90.3 | 29.8 | 29.2 | 0.85 | 1.01 | 2 | 1 | 0.4 | 0.2 | 340 | 274 |
| P18 | 91 | 88.2 | 30.4 | 29.5 | 0.9 | 0.83 | 7 | 6 | 1.6 | 1.2 | 280 | 221 |
| P19 | 94.5 | 89.4 | 28.4 | 26.9 | 0.79 | 0.77 | 5 | 4 | 1.0 | 0.8 | 259 | 191 |
| P20 | 102.4 | 101.9 | 32.4 | 32.2 | 1.01 | 0.88 | 23 | 18 | 5.7 | 3.9 | 279 | 213 |
| P21 | 94.1 | 90.6 | 29.1 | 28.0 | 0.92 | 0.85 | 13 | 6 | 3.0 | 1.3 | 245 | 225 |
| P22 | 91.1 | 89.5 | 32.7 | 32.1 | 1.1 | 0.88 | 8 | 6 | 2.2 | 1.3 | 394 | 274 |
P1 to P22- ID multiple ascending dose (MAD) participants ; cohort (Coh.) of participants; ND, not determinated; P value (P) obtained performing paired t-test statistical analyses compairing day 1 vs day 15
Demographic characteristics of volunteers in SAD and MAD studies and baseline-to-end (Day 1 to Day 15) treatment profile of MAD cohorts.