Study to Evaluate Single Inhaled Doses of PT001, PT003, PT005 and PT001 Plus PT005 in Healthy Subjects

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: PT003
Drug: PT001 + PT005
Drug: PT005
Drug: PT001

Registration Number: NCT00893971

Lead Sponsor: Pearl Therapeutics, Inc.

Brief Summary: The purpose of this study is to evaluate the safety of a single dose of PT003 compared with single doses of PT001 and PT005, and compared with PT001 plus PT005 delivered together as two separate single doses in healthy subjects.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Provide signed written informed consent
18-55 years of age
Healthy subjects confirmed by medical history, physical examination, vital signs, pulmonary function tests, electrocardiogram and clinical laboratory tests
Female subjects of child-bearing potential who are sexually active must be willing to undergo a pregnancy test and agree to use two forms of contraception
Body mass index (BMI) between 18.5 and 30, inclusive
Non-smokers for at least 6 months prior to screening
Pulmonary function tests within normal limits
Willing to remain at the study center for at least 12-24 hours on each test day
Venous access in both arms to allow collection of numerous blood samples

Exclusion Criteria

Women who are pregnant or lactating
Clinically significant medical conditions
Viral illness within the last 30 days
Symptomatic prostatic hypertrophy or bladder neck obstruction
Known narrow-angle glaucoma
History of bowel obstruction
Clinically significant abnormal electrocardiogram
Positive Hepatitis B surface antigen or positive Hepatitis C antibody
Positive screening test for HIV antibodies
History of hypersensitivity to any beta2-agonists, anticholinergics, or any component of the MDI
Known or suspected history of alcohol or drug abuse within the last 2-years
Greater than normal alcohol consumption
Ingestion of any poppy seeds within the 48 hours prior to the screening
Ingestion of any poppy seeds within the 48 hours prior to, or any alcohol, xanthines or grapefruit-containing foods or beverages within the 24 hours prior to, or during, each confinement
Positive breath alcohol result
Positive urine drug screen
Use of any beta2-agonists,or anticholinergics prior to the recruitment interview
Lower respiratory tract infections requiring antibiotics in the previous 6 weeks
Use of any other prescription medication
Use of any over the counter product, herbal product, diet aid, hormone supplement
Donation > 450 ml of blood within 8 weeks of first treatment dose
Clinically significant vital sign abnormality
Clinically significant biochemical, hematological or urinalysis abnormality
Affiliations with investigator site
Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives prior to screening, whichever is longer

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
3	PT003	Inhaled PT003 (PT001 18 μg / 2.4 μg PT005)
4	PT001 + PT005	PT001 18 μg + PT005 2.4 μg
2	PT005	Inhaled PT005 2.4 μg
1	PT001	Inhaled PT001 18 μg

Primary Outcome Measures

Name	Time	Method
Symptoms of Dry Mouth	12 hours	Number of participants reporting dry mouth at 12 hours post-dose
ECG Change From Baseline	12 hours	Change from baseline for ECG parameters 12-hours post-dose
Spirometry Change From Baseline	12 hours	Change from baseline for spirometery measures 12-hours post-dose PEFR (L/min)
Serum Potassium Change From Baseline	12 hours
Symptoms of Tremor	12 hours	Number of participants reporting tremor at 12 hours post-dose
Blood Chemistry Change From Baseline	24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects	Series of 11 blood chemistries assessed throughout the study
Hematology Change From Baseline	24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects	Hematology assessments taken throughout the study Hemoglobin
Heart Rate Change From Baseline	12 hours	Change from baseline for heart rate 12-hours post-dose Heart rate (bpm)
Vital Sign Change Baseline; Blood Pressure	12 hours	Vital sign change baseline; blood pressure
Vital Sign Change From Baseline, SpO2	12 hours	Vital Sign Change from baseline 12-hours post-dose SpO2 (%)

Secondary Outcome Measures

Name	Time	Method
Plasma Glycopyrrolate PK Parameters	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma glycopyrrolate
Plasma Glycopyrrolate PK Parameters AUC0-inf (h*pg/mL)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma glycopyrrolate
Plasma Glycopyrrolate PK Parameters (Tmax)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma glycopyrrolate
Plasma Glycopyrrolate PK Parameters (t1/2)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma glycopyrrolate
Plasma Glycopyrrolate PK Parameters Cmax (pg/mL)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma glycopyrrolate
Plasma Glycopyrrolate PK Parameters (ke)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma glycopyrrolate
Plasma Formoterol PK Parameters	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma formoterol
Plasma Formoterol PK Parameters AUC0-inf (h*pg/mL)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma formoterol
Plasma Formoterol PK Parameters (Tmax)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma formoterol
Plasma Formoterol PK Parameters (t1/2)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Various pharmacokinetic parameters for plasma formoterol
Plasma Formoterol PK Parameters (Cmax)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Pharmacokinetic parameters for plasma formoterol Cmax
Plasma Formoterol PK Parameters (ke)	Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose	Pharmacokinetic parameters for plasma formoterol ke