Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 24 of 205 for:    SPORANOX I.V. OR ITRACONAZOLE OR ONMEL OR SPORANOX-PULSE OR Sporanos OR R 51,211 OR SPORANOX

A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics (PK) of Nemiralisib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03398421
Recruitment Status : Completed
First Posted : January 12, 2018
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: Nemiralisib Drug: Itraconazole Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Subjects will receive nemiralisib alone on Day 1 in Period 1 and itraconazole from Day 1 to Day 10 followed by nemiralisib on Day 5 in Period 2.
Masking: None (Open Label)
Masking Description: This will be an open-label study. Hence, there will be no masking.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 17, 2018
Actual Primary Completion Date : March 12, 2018
Actual Study Completion Date : March 12, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Subjects receiving nemiralisib and itraconazole
Eligible subjects will receive a single dose of 100 micrograms (mcg) nemiralisib on Day 1 in Period 1. Subjects will also receive a single dose of 200 milligrams (mg) itraconazole in the morning from Day 1 to Day 10 and single dose of 100 mcg nemiralisib on Day 5, one hour after the dose of itraconazole in Period 2. There will be a washout of at least 14 days between the administration of nemiralisib in Period 1 and Period 2.
Drug: Nemiralisib
Nemiralisib will be given as 100 mcg via ELLIPTA Dry Powder Inhaler with 30 doses per inhaler/ 100 mcg total dose. ELLIPTA® is a registered trademark of GlaxoSmithKline group of companies.

Drug: Itraconazole
Itraconazole will be given as 100 mg per capsule per day administered orally with water




Primary Outcome Measures :
  1. Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-infinity]) of nemiralisib following administration of itraconazole in Period 2 [ Time Frame: Pre-dose, and 5, 30 minutes, 2 , 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of nemiralisib following repeat doses of itraconazole.

  2. Area under the plasma concentration versus time curve from time zero to t (AUC [0-t]) of nemiralisib following administration of itraconazole in Period 2 [ Time Frame: Pre-dose, and 5, 30 minutes, 2 , 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of nemiralisib following repeat doses of itraconazole.

  3. Maximum observed plasma concentration (Cmax) of nemiralisib following administration of itraconazole in Period 2 [ Time Frame: Pre-dose, and 5, 30 minutes, 2 , 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of nemiralisib following repeat doses of itraconazole

  4. Time to Cmax (Tmax) of nemiralisib following administration of itraconazole in Period 2 [ Time Frame: Pre-dose, and 5, 30 minutes, 2 , 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of nemiralisib following repeat doses of itraconazole.

  5. Terminal phase half-life (T1/2) of nemiralisib following administration of itraconazole in Period 2 [ Time Frame: Pre-dose, and 5, 30 minutes, 2 , 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of nemiralisib following repeat doses of itraconazole


Secondary Outcome Measures :
  1. Number of subjects with adverse events (AEs) [ Time Frame: Up to 41 days ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

  2. Number of subjects with serious AEs (SAEs) [ Time Frame: Screening and up to 41 days ]
    Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

  3. Number of subjects with abnormal clinical chemistry laboratory parameters [ Time Frame: Up to 41 days ]
    Clinical chemistry parameters will be analyzed as a measure of safety including blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct bilirubin, creatinine, sodium, alanine aminotransferase (ALT)/Serum Glutamic-Pyruvic Transaminase (SGPT), total protein, glucose, calcium and alkaline phosphatase.

  4. Number of subjects with abnormal hematology laboratory parameters [ Time Frame: Up to 41 days ]
    Hematology parameters will be analyzed as a measure of safety including platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, percent reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  5. Number of subjects with abnormal values for urinalysis [ Time Frame: Up to 30 days ]
    Urinalysis parameters will be analyzed including specific gravity. The dipstick method will be used to analyze potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase. Microscopic examination will be performed if blood or protein is abnormal.

  6. Number of subjects with abnormal values for blood pressure [ Time Frame: Up to 30 days ]
    Systolic and diastolic blood pressure will be measured in a supine or semi-supine position after 5 minutes rest.

  7. Number of subjects with abnormal values for body temperature [ Time Frame: Up to 30 days ]
    Body temperature will be measured in a supine or semi-supine position after at least a 5 minutes rest.

  8. Number of subjects with abnormal pulse rate [ Time Frame: Up to 30 days ]
    Pulse rate will be measured in a supine or semi-supine position after 5 minutes rest.

  9. Number of subjects with abnormal respiratory rate [ Time Frame: Up to 30 days ]
    Respiratory rate will be measured in a supine or semi-supine position after at least a 5 minutes rest.

  10. Number of subjects with abnormal electrocardiogram (ECG) findings [ Time Frame: Up to 41 days ]
    A 12-lead ECGs will be measured in a supine or semi-supine position after 5 minutes rest at each time point using ECG machine.

  11. Forced expiratory volume in 1 second (FEV1) following doing with nemiralisib when dosed alone and concomitantly with itraconazole [ Time Frame: Up to Day 4 ]
    FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 is a measure of lung function which will be assessed by spirometry.

  12. AUC (0-infinity) of itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of itraconazole when co-administered with nemiralisib.

  13. AUC (0-infinity) of hydroxy-itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of hydroxy-itraconazole when co-administered with nemiralisib.

  14. AUC (0-t) of itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of itraconazole when co-administered with nemiralisib.

  15. AUC (0-t) of hydroxy-itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of hydroxy-itraconazole when co-administered with nemiralisib.

  16. Cmax of itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of itraconazole when co-administered with nemiralisib.

  17. Cmax of hydroxy-itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of hydroxy-itraconazole when co-administered with nemiralisib.

  18. Tmax of itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of itraconazole when co-administered with nemiralisib.

  19. Tmax of hydroxy-itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of hydroxy-itraconazole when co-administered with nemiralisib.

  20. T1/2 of itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of itraconazole when co-administered with nemiralisib.

  21. T1/2 of hydroxy-itraconazole when co-administered with nemiralisib in Period 2 [ Time Frame: Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and Day 5; 24 hours post-dose on Day 5 ]
    Blood samples will be collected for pharmacokinetic analysis of hydroxy-itraconazole when co-administered with nemiralisib.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03398421


Locations
Layout table for location information
United States, Kansas
GSK Investigational Site
Overland Park, Kansas, United States, 66211
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Study Director: GSK Clinical Trials GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] December 12, 2017
Statistical Analysis Plan  [PDF] April 12, 2018


Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03398421     History of Changes
Other Study ID Numbers: 206874
First Posted: January 12, 2018    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Nemiralisib
Pharmacokinetics
Itraconazole
Drug-drug Interaction
Cross-over

Additional relevant MeSH terms:
Layout table for MeSH terms
Itraconazole
Hydroxyitraconazole
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors