Summary of pharmacokinetic results from clinical studies performed with linaclotide
The clinical protocols and all clinical trial procedures were approved by an institutional review board, and the trial was designed, conducted, and reported in accordance with the principles of good clinical practice guidelines. All patients gave written informed consent before their participation in the trial.
| Study Number | Linaclotide Doses (Number of PK Subjects) | Linaclotide Plasma Concentrations | MM-419447 Plasma Concentrations |
|---|---|---|---|
| PK STUDIES IN HEALTHY VOLUNTEERS | |||
| MCP-103-001 (phase 1, U.S.) | Single | Not detectable (<3.00 ng/ml) | Not detectable (<3.00 ng/ml) |
| 29 μg (4); 97 μg (8); 290 μg (4); 966 μg (4); 2897 μg (4) | |||
| 0456-CL-0011 (phase 1, Japan) | Single | Not detectable (<0.200 ng/ml) | Not detectable (<2.00 ng/ml) |
| 109 μg (6); 327 μg (6); 1090 μg (6); 3270 μg (6) | |||
| MCP-103-002 (phase 1, U.S.) | QD × 7 days | Not detectable (<3.00 ng/ml) | Not detectable (<3.00 ng/ml) |
| 29 μg (8); 97 μg (8); 290 μg (8); 966 μg(8) | |||
| MCP-103-103 (phase 1 food effect, U.S.) | QD × 7 days | Not detectable (<0.200 ng/ml) | Not detectable (<2.00 ng/ml) |
| 290 μg (9 fed, 10 fasted) | |||
| Single | Not detectable (<0.200 ng/ml) except in 2 fasted subjects | Not detectable (<2.00 ng/ml) | |
| 2897 μg (9 fed, 9 fasted) | Subject 12 Cmax = 0.735 ng/ml | ||
| Subject 19 Cmax = 0.212 ng/ml | |||
| SPARSE SAMPLING (DAY 1 AND 29) IN PATIENTS WITH CIC | |||
| LIN-MD-01 (phase 3) | QD × 12 weeks | Not detectable (<0.200 ng/ml) | Not detectable (<2.00 ng/ml) |
| 145 μg (51); 290 μg (53) | |||
| MCP-103-303 (phase 3) | QD × 12 weeks | Not detectable (<0.200 ng/ml) | Not detectable (<2.00 ng/ml) |
| 145 μg (101); 290 μg (98) | |||
| SPARSE SAMPLING (DAY 1 AND 29) IN PATIENTS WITH IBS-C | |||
| LIN-MD-31 (phase 3) | QD × 12 weeks | Not detectable (<0.200 ng/ml) | Not detectable (<2.00 ng/ml) |
| 290 μg (64) | |||
| MCP-103-302 (phase 3) | QD × 26 weeks | Not detectable (<0.200 ng/ml) except in 2 patients on day 1 | Not detectable (<2.00 ng/ml) |
| 290 μg (98) | Patient 007-2006 = 0.241 ng/ml | ||
| Patient 049-2006 = 0.239 ng/ml | |||
CIC, chronic idiopathic constipation; IBS-C, irritable bowel syndrome with constipation; QD, every day; PK, pharmacokinetics study.