A Thorough QT Study of Teduglutide in Healthy Subjects.
Teduglutide, an analog of the endogenous hormone glucagon-like peptide-2, is currently being developed for the treatment of short bowel syndrome. This study investigated the potential effects of teduglutide on cardiac conduction and repolarization. Seventy-two healthy volunteers underwent 4 treatment periods in randomized order with a single subcutaneous injection of placebo, 5 and 20 mg teduglutide, and a single oral 400-mg dose of moxifloxacin. The primary variable to investigate the effect on cardiac repolarization was the difference between QTcF after administration versus predose. The observed upper bounds of the 95% one-sided confidence intervals were 3.0 ms (5 mg) and 4.5 ms (20 mg). Arithmetic mean curves of QTcF intervals over time of both doses of teduglutide and of placebo were almost superposable. Assay sensitivity for the positive control moxifloxacin was shown. In conclusion, teduglutide at intended therapeutic and supratherapeutic doses had no effect on cardiac repolarization. No safety concerns were identified. Treatment with teduglutide was well tolerated.
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Manfred
M
Hartmann
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Wolfgang
W
Timmer
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Armin
A
Schultz
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Rüdiger
R
Nave
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Reinhold
R
Luehmann
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Stephan
S
Krause
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Gezim
G
Lahu
Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, GermanyCRS Clinical Research Services, Mannheim GmbH, Mannheim, Germany.
Joachim
J
Scholpp
QTc interval; gastrointestinal; peptides; pharmacodynamics; pharmacokinetics