A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics (PK) of Nemiralisib
| Status: | Completed |
|---|---|
| Conditions: | Chronic Obstructive Pulmonary Disease, Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 1/17/2019 |
| Start Date: | January 17, 2018 |
| End Date: | March 12, 2018 |
A Single Centre, Open Label, One Sequence, Cross-over Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Single Inhaled Doses of Nemiralisib in Healthy Subjects
Nemiralisib is a potent anti-inflammatory agent for the treatment of chronic obstructive
pulmonary disease (COPD) and other inflammatory lung diseases. The Cytochrome P450 3A4
(CYP3A4) is a major route of clearance for nemiralisib. The co-administration of drug
therapies, which modulate CYP3A4, may alter the exposure of nemiralisib. Hence, this clinical
drug interaction study with itraconazole (a potent CYP3A4 inhibitor) is required. The study
will evaluate the PK, safety and tolerability of nemiralisib when administered alone and when
administered concomitantly with repeat doses of itraconazole in healthy males and females.
Subjects will receive treatment with nemiralisib alone in Period 1 and itraconazole followed
by nemiralisib in Period 2 in single sequence crossover manner. Approximately 20 subjects
will be enrolled such that approximately 16 evaluable subjects complete the study. Each
subject will participate in the study for approximately 7 weeks including screening visit, 2
treatment periods and a follow up visit.
pulmonary disease (COPD) and other inflammatory lung diseases. The Cytochrome P450 3A4
(CYP3A4) is a major route of clearance for nemiralisib. The co-administration of drug
therapies, which modulate CYP3A4, may alter the exposure of nemiralisib. Hence, this clinical
drug interaction study with itraconazole (a potent CYP3A4 inhibitor) is required. The study
will evaluate the PK, safety and tolerability of nemiralisib when administered alone and when
administered concomitantly with repeat doses of itraconazole in healthy males and females.
Subjects will receive treatment with nemiralisib alone in Period 1 and itraconazole followed
by nemiralisib in Period 2 in single sequence crossover manner. Approximately 20 subjects
will be enrolled such that approximately 16 evaluable subjects complete the study. Each
subject will participate in the study for approximately 7 weeks including screening visit, 2
treatment periods and a follow up visit.
Inclusion Criteria:
- Subjects must be 18 to 75 years of age inclusive, at the time of signing the informed
consent.
- Subjects who are overtly healthy as determined by medical evaluation including medical
history, physical examination, laboratory tests, and cardiac evaluation.
- Normal spirometry at Screening (FEV1 and forced vital capacity [FVC] >=80 percent of
predicted. Measurements to be taken in triplicate. The highest value of each
individual component must be >=80 percent of predicted).
- A subject with a clinical abnormality or laboratory parameter(s) (except for liver
function tests) outside the reference range for the population being studied may be
included only if the investigator, in consultation with the medical monitor if needed,
agree and document that the finding is unlikely to introduce additional risk factors
and will not interfere with the study procedures.
- Body weight >50 kilograms (kg) and body mass index (BMI) within the range 18.0-35.0 kg
per meter square (kg/m^2) (inclusive).
- Male and/or female: A male subject must agree to use contraception during the
treatment period and for at least 10 days after the last dose of study treatment and
refrain from donating sperm during this period; a female subject is eligible to
participate if she is not pregnant, not breastfeeding, and not a woman of childbearing
potential (WOCBP).
- Capable of giving signed informed consent.
Exclusion Criteria:
- History or presence of cardiovascular, respiratory (except childhood asthma, which has
now remitted), hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric
or neurological disorders capable of significantly altering the absorption,
metabolism, or elimination of drugs; constituting a risk when taking the study
treatment; or interfering with the interpretation of data.
- Abnormal blood pressure.
- Liver function test results above the upper limit of normal (ULN).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT interval corrected for heart rate by Fridericia's formula (QTcF) >450 milliseconds
(msec).
- Past or intended use of over-the-counter or prescription medication including herbal
medications within 14 days prior to dosing.
- Participation in the study would result in loss of blood or blood products in excess
of 500 milliliter (mL) within 90 days.
- Exposure to more than 4 new chemical entities within 12 months prior to the first
dosing day.
- Current enrolment or past participation within the last 30 days before signing of
consent in this or any other clinical study involving an investigational study
treatment or any other type of medical research.
- Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C
antibody test result at screening.
- Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3
months prior to first dose of study treatment.
- Positive human immunodeficiency virus (HIV) antibody test (according to local
policies).
- Positive drug/alcohol test at screening or on admission (Day -1).
- Regular use of known drugs of abuse.
- Regular alcohol consumption within 6 months prior to the study defined as: an average
weekly intake of >14 drinks for males or >7 drinks for females. One drink is
equivalent to 12 grams (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL)
of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or
nicotine-containing products within 6 months of screening, or a total pack year
history of >5 pack years. [number of pack years = (number of cigarettes per day/20) x
number of years smoked].
- Sensitivity to any of the study treatments, or components thereof (including lactose
and Magnesium Stearate), or drug or other allergy that, in the opinion of the
investigator or medical monitor, contraindicates participation in the study.
- Unwillingness to follow the lifestyle restrictions.
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