Pharmacokinetics and Safety Study of PT010 and PT003 in Healthy Chinese Adult Subjects

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Phase I, Randomized, Double-Blind, Parallel-Group, Study to Assess the Pharmacokinetics and Safety of Two Doses of PT010 and a Single Dose of PT003 in Healthy Chinese Adult Subjects Following A Single Administrations and After Chronic Administration for 7 Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03075267
• Other study ID #: PT010010
• Status: Completed
• Phase: Phase 1
• Start date: April 17, 2017
• Est. completion date: September 5, 2017

Study information

• Verified date: December 2020
• Source: Pearl Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to assess the pharmacokinetics and safety of two doses of PT010 and a single dose of PT003 in healthy Chinese adult subjects

Description:

A Phase I, Randomized, Double-Blind, Parallel Group, Study to Assess the Pharmacokinetics and Safety of Two Doses of PT010 and a Single Dose of PT003 in Healthy Chinese Adult Subjects Following a Single Administration and After Chronic Administration for 7 Days

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: September 5, 2017
• Est. primary completion date: September 5, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Male and female Chinese subjects 18-45 years of age

• Females of childbearing potential must agree to be abstinent or else use one of the medically acceptable forms of contraception A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception.

A male subject with female partner of child bearing potential must agree to use one additional form of medically acceptable contraception

-Be in good general health as assessed at Screening and have no clinically significant abnormal labs at Screening.

Exclusion Criteria:

• Pregnant or nursing female subjects or subjects who are trying to conceive

• Subjects with clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic, pulmonary, hematological, psychiatric, or other medical illness that would interfere with participation in this study

• Subjects with a history of ECG abnormalities

• Subjects who have cancer that has not been in complete remission for at least 5 years

• Male subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator

• Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Screening

• Males with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator

• Subjects with a diagnosis of glaucoma that in the opinion of the Investigator has not been adequately treated

• History of substance-related disorders within 1 year of Screening

• History of smoking or the use of nicotine containing products or electronic cigarettes within 3 months of Screening by self-reporting

• A positive alcohol breathalyzer or urine drug screen for drugs of abuse at the Screening Visit or at the beginning of each inpatient period

• Treatment with any prescription or non-prescription drugs (including vitamins, herbal, and dietary supplements) within 30 days

• Positivity for human immunodeficiency virus (HIV) or Hepatitis B surface antigen (HbsAg) or positive hepatitis C antibody at Screening

• Positive for Syphilis Antibody

• Subjects with any flu-like syndrome or other respiratory infections

• Recently vaccinated with an attenuated live virus

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• PT010 (BGF MDI) 320/14.4/9.6 µg
A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.
• PT010 (BGF MDI) 160/14.4/9.6 µg
A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.
• PT003 (GFF MDI) 14.4/9.6 µg
A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.

Locations

Country	Name	City	State
China	Research Site	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Pearl Therapeutics, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax) - Budesonide	Maximum plasma concentration (Cmax) of Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Maximum Plasma Concentration (Cmax) - Budesonide	Maximum plasma concentration (Cmax) of Budesonide Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Maximum Plasma Concentration (Cmax) - Glycopyrronium	Maximum plasma concentration (Cmax) of Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Maximum Plasma Concentration (Cmax) - Glycopyrronium	Maximum plasma concentration (Cmax) of Glycopyrronium Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Maximum Plasma Concentration (Cmax) - Formoterol	Maximum plasma concentration (Cmax) of Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Maximum Plasma Concentration (Cmax) - Formoterol	Maximum plasma concentration (Cmax) of Formoterol Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 8	Day 8
Primary	Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 1	Day 1
Primary	Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 8	Day 8
Primary	Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 1	Day 1
Primary	Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 8	Day 8
Primary	Time to Maximum Plasma Concentration (Tmax) - Budesonide	Time to maximum plasma concentration (tmax) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Time to Maximum Plasma Concentration (Tmax) - Budesonide	Time to maximum plasma concentration (tmax) - Budesonide Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium	Time to maximum plasma concentration (tmax) - Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium	Time to maximum plasma concentration (tmax) - Glycopyrronium Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Time to Maximum Plasma Concentration (Tmax) - Formoterol	Time to maximum plasma concentration (tmax) - Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Time to Maximum Plasma Concentration (Tmax) - Formoterol	Time to maximum plasma concentration (tmax) - Formoterol Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Budesonide	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Budesonide Day 1	Day 1
Primary	Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Glycopyrronium Day 1	Day 1
Primary	Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Formoterol Day 1	Day 1
Primary	Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-8) - Budesonide	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-8) - Budesonide Day 1	Day 1
Primary	Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-8) - Glycopyrronium	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-8) - Glycopyrronium Day 1	Day 1
Primary	Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-8) - Formoterol	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-8) - Formoterol Day 1	Day 1
Primary	Elimination Half-life (t½) - Budesonide	Elimination half-life (t½) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Elimination Half-life (t½) - Glycopyrronium	Elimination half-life (t½) - Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Elimination Half-life (t½) - Formoterol	Elimination half-life (t½) - Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Apparent Total Body Clearance (CL/F) - Budesonide	Apparent total body clearance (CL/F) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Apparent Total Body Clearance (CL/F) - Glycopyrronium	Apparent total body clearance (CL/F) - Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Apparent Total Body Clearance (CL/F) - Formoterol	Apparent total body clearance (CL/F) - Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Apparent Volume of Distribution (Vd/F) - Budesonide	Apparent volume of distribution (Vd/F) - Budesonide - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Apparent Volume of Distribution (Vd/F) - Glycopyrronium	Apparent volume of distribution (Vd/F) - Glycopyrronium - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Apparent Volume of Distribution (Vd/F) - Formoterol	Apparent volume of distribution (Vd/F) - Formoterol - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Terminal Elimination Rate Constant (?z) - Budesonide	Terminal elimination rate constant (?z) - Budesonide - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Terminal Elimination Rate Constant (?z) - Glycopyrronium	Terminal elimination rate constant (?z) - Glycopyrronium - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Terminal Elimination Rate Constant (?z) - Formoterol	Terminal elimination rate constant (?z) - Formoterol - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Accumulation Ratio for Cmax (RAC [Cmax]) - Budesonide	Accumulation ratio for Cmax (RAC [Cmax]) - Budesonide	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium	Accumulation ratio for Cmax (RAC [Cmax]) - Glycopyrronium	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Primary	Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol	Accumulation ratio for Cmax (RAC [Cmax]) - Formoterol	Day 1 and Day 8
Primary	Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide	Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide	Day 1 and Day 8
Primary	Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium	Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium	Day 1 and Day 8
Primary	Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol	Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol	Day 1 and Day 8
Secondary	Physical Exam Findings	Number of subjects with clinically significant changes in post baseline physical exam findings	Visit 4, Day 8
Secondary	Laboratory Tests	Number of subjects with clinically significant changes in post baseline laboratory tests	Visit 4, Day 8
Secondary	Electrocardiogram	Number of subjects with clinically significant changes in post baseline electrocardiogram	Visit 4, Day 8
Secondary	Serious Adverse Events/Adverse Events	Number of subjects with clinically significant changes in post baseline serious TEAEs (treatment-emergent adverse events) or TEAEs leading to withdrawal	Visit 4, Day 8
Secondary	Vital Signs	Number of subjects with clinically significant changes in post baseline vital signs	Visit 4, Day 8

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