Safety and efficacy of the sodium-glucose cotransporter 1 inhibitor mizagliflozin for functional constipation: a randomised, placebo-controlled, double-blind phase 2 trial
| Autor: | Makoto Yamamura, Tomohiro Tada, Hiroyuki Kobayashi, Toshio Nakajima, Tatsuhiro Oishi, Tetsuo Ooshima, Yoshinori Yagi, Tatsuhiko Usui, Takashi Yamamoto, Atsushi Nakajima, Shigeru Shirota, Yamasaki Syuji, Michio Hongo, Tatsuya Abe, Hideo Sawada, Yutaka Segawa, Kotaro Ozawa, Shigeyasu Kamata, Takashi Majima, Tomohiro Nakata, Yuka Endo, Norimichi Yamada, Kohei Kaku, Ryoichi Suzuki, Shin Fukudo, Yasuhiro Nagaoka, Hidenori Kurakata, Etsuro Shoji, Shinichi Miyazaki, Ken Tarumi, Hiroaki Tanaka, Katsuhiko Nakai, Seiji Otsuka, Hiroshi Ishii, Kanako Sameshima |
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| Rok vydání: | 2018 |
| Předmět: |
education.field_of_study
medicine.medical_specialty Hepatology business.industry Population Gastroenterology Placebo medicine.disease law.invention Clinical trial 03 medical and health sciences 0302 clinical medicine Tolerability Randomized controlled trial law 030220 oncology & carcinogenesis Internal medicine medicine Defecation Outpatient clinic Functional constipation 030211 gastroenterology & hepatology education business |
| Zdroj: | The Lancet Gastroenterology & Hepatology. 3:603-613 |
| ISSN: | 2468-1253 |
| DOI: | 10.1016/s2468-1253(18)30165-1 |
| Popis: | Summary Background Mizagliflozin is a novel oral sodium-glucose cotransporter 1 (SGLT1) inhibitor that increases luminal glucose and water. This study assessed the efficacy and safety of mizagliflozin in patients with functional constipation. Methods In this multicentre, randomised, double-blind phase 2 trial at 32 hospitals and community outpatient clinics in Japan, we enrolled patients with functional constipation or constipation-predominant irritable bowel syndrome, aged 20 years or older. Patients were randomly assigned (1:1:1), by use of an independent centralised registration system and dynamic allocation method, to receive mizagliflozin 5 mg, mizagliflozin 10 mg, or placebo, orally once daily for 4 weeks. Patients, investigators, staff, and the sponsor were blinded to the group assignments. The primary outcome was the change from baseline in the number of spontaneous bowel movements per week after 1 week. Efficacy analysis was done in all patients except those who deviated from good clinical practice, did not receive at least one dose of the study drug, withdrew before starting treatment, were ineligible, or for whom the primary outcome could not be assessed, and safety was assessed in all patients except those who deviated from good clinical practice, who did not receive the study drug, or who withdrew before receiving treatment. This trial is registered with ClinicalTrials.gov , number NCT02281630 , and is completed. Findings Between Oct 15, 2014, and March 7, 2015, 258 patients with functional constipation were randomly assigned: 86 patients per group. Two patients from the placebo group and three from the 10 mg mizagliflozin group were excluded because the primary outcome could not be assessed, and one patient from the 5 mg mizagliflozin group was excluded for not receiving the study drug; therefore 84 patients in the placebo group, 85 in the 5 mg mizagliflozin group, and 83 in the 10 mg mizagliflozin group were included in the full analysis population. Mean change from baseline in the number of spontaneous bowel movements per week after 1 week with mizagliflozin 5 mg (3·85 [SD 3·96]) and mizagliflozin 10 mg (5·85 [6·01]) was significantly greater than those in the placebo group (1·80 [1·80]; p Interpretation The SGLT1 inhibitor mizagliflozin showed favourable efficacy and tolerability at 5 mg and 10 mg doses in patients with functional constipation, providing a potential alternative therapy to available drugs. Funding Kissei Pharmaceutical. |
| Databáze: | OpenAIRE |
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