This was a saftey study of TAK-375 16 mg and a placebo taken once daily for two days in
subjects with chronic obstructive pulmonary disease (COPD).
Inclusion Criteria:
- Females of childbearing potential were nonpregnant and nonlactating and used
appropriate birth control for the study duration.
- The subject had a clinical history of COPD and a confirmatory diagnosis based on PFTs
at Screening, with mild to moderate airflow limitation
- The subject had a postbronchodilator FEV1 change from Baseline of less than 12%.
- The subject had a negative chest X-ray at Screening, other than findings consistent
with mild to moderate COPD, within the last 6 months.
- The subject had a SaO2 during sleep greater than 85% for at least 99% of the recording
period with no SaO2 readings less than 80% as assessed by pulse oximetry at PSG
Screening.
- The subject had a SaO2 during wakefulness greater than 91% (both supine and sitting)
as assessed by pulse oximetry at Screening.
- The subject's habitual bedtime was between 8: 30 PM and 12: 00 AM.
Exclusion Criteria:
- The subject had a known hypersensitivity to TAK-375 or related compounds, including
melatonin.
- The subject had a known hypersensitivity to albuterol or related compounds.
- The subject had previously participated in a study involving TAK-375.
- The subject had participated in any other investigational study, or taken any
investigational drug within 30 days or 5 half lives prior to the first dose of study
medication, whichever was longer.
- The subject had a clinical history of acute or chronic respiratory failure, severe
COPD, or hypercapnia (PaO2 greater than or equal to 45 mm Hg).
- The subject had a history of or currently had right ventricular hypertrophy on ECG or
right heart failure.
- The subject had periodic leg movement (PLM) with arousal index (per hour of sleep)
greater than 20 as seen on the first night of the PSG Screening.
- The subject had AHI (per hour of sleep) greater than 15 as determined by PSG during
the PSG Screening night.
- The subject had an acute clinically significant illness within 2 weeks or had been
hospitalized within 4 weeks of study participation.
- The subject had sleep schedule changes required by employment (ie, shift work) within
3 months prior to Day 1 of study medication, or had flown across greater than 3 time
zones within 7 days prior to Screening.
- The subject had participated in a weight loss program or has substantially altered
their exercise routine within 30 days prior to Day 1 of study medication.
- The subject had a history of seizures, sleep apnea, restless leg syndrome, PLM
disorder, other known sleep disorders, schizophrenia, bipolar disease, mental
retardation, or cognitive disorder.
- The subject had a history of psychiatric disorder (including anxiety or depression)
within the past 12 months.
- The subject was unable to discontinue the use of hypnotics (other than study drug) for
the duration of the study.
- The subject used melatonin or other drugs or supplements known to affect sleep wake
function within 1 week (or 5 half lives of the drug, whichever was longer) prior to
Day 1 of study medication.
- The subject used any CNS medication within 1 week (or 5 half lives of the drug,
whichever was longer) prior to Day 1 of study medication. These medications must not
have been used to treat psychiatric disorders.
