A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010

Phase 1

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: Regimen A
Drug: Regimen B
Drug: Regimen C
Drug: Regimen D

Registration Number: NCT03311373

Lead Sponsor: Pearl Therapeutics, Inc.

Brief Summary: Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010

Detailed Description: A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010 Administered With and Without a Spacer, and With and Without Oral Charcoal

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

Inclusion Criteria

Signed and dated Independent Ethics Committee (IEC)/Institutional Review Board (IRB)-approved Informed Consent Form (ICF) before any protocol-specific screening procedures are performed
Male and female subjects 18 to 40 years of age, inclusive
Be in good general health as determined by a thorough medical history and physical examination, ECG, vital signs, and clinical laboratory evaluation
Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal, or surgically sterile
Male subjects who are sexually active must agree to use a double-barrier method of contraception (condom with spermicide) from the first dose of randomized study drug until 2 weeks after their last dose, and must not donate sperm during their study participation period
Screening laboratory tests must be within normal range or determined to not be clinically significant by the Investigator.
Demonstrate correct MDI administration technique

Key

Exclusion Criteria

For female subjects, a positive serum human chorionic gonadotropin (hCG) test at screening or a positive urine hCG at admission for any of the 4 Treatment Periods
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 who have cancer that has not been in complete remission for at least 5 years
Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to screening
Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator
History of substance-related disorders (with the exception of caffeine-related and nicotine-related disorders) within 1 year of screening
History of smoking or the use of nicotine-containing products within 3 months of screening by self-reporting
A positive alcohol breathalyzer or urine drug screen for drugs of abuse at screening or at the beginning of each Treatment Period
Treatment with any prescription or non-prescription drugs including vitamins, herbal, and dietary supplements for 28 days or 5 half-lives, whichever is longer, before study drug use
Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the beginning of the screening Period
Subjects with any flu-like syndrome or other respiratory infections within 2 weeks of drug administration or who have been vaccinated with an attenuated live virus within 4 weeks of drug administration
Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for the study (eg, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Period 4	Regimen C	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 1	Regimen B	Test Formulation (Regimen B or D) or Reference Formulation (Regimen A or C)
Treatment Period 3	Regimen B	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 3	Regimen C	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 4	Regimen D	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 1	Regimen C	Test Formulation (Regimen B or D) or Reference Formulation (Regimen A or C)
Treatment Period 3	Regimen D	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 4	Regimen A	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 2	Regimen B	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 2	Regimen D	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 1	Regimen A	Test Formulation (Regimen B or D) or Reference Formulation (Regimen A or C)
Treatment Period 1	Regimen D	Test Formulation (Regimen B or D) or Reference Formulation (Regimen A or C)
Treatment Period 2	Regimen A	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 2	Regimen C	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 3	Regimen A	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)
Treatment Period 4	Regimen B	Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)

Primary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax)-Budesonide	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Maximum plasma concentration (Cmax) per Regimen
Maximum Plasma Concentration (Cmax)-Formoterol	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Maximum plasma concentration (Cmax) per Regimen
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen
Maximum Plasma Concentration (Cmax)-Glycopyrronium	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Maximum plasma concentration (Cmax) per Regimen
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen

Secondary Outcome Measures

Name	Time	Method
Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen
Time to Maximum Plasma Concentration (Tmax)-Budesonide	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol	24 hrs	Each treatment period is equal to assigned regimen
Time to Maximum Plasma Concentration (Tmax)-Formoterol	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose	Each treatment period is equal to assigned regimen