Healthy Volunteers
Conditions
Keywords
Healthy Volunteers
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.
Interventions
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms of Dry Mouth | 12 hours | Number of participants reporting dry mouth at 12 hours post-dose |
| 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 Hematocrit |
| 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 (%) |
| ECG Change From Baseline | 12 hours | Change from baseline for ECG parameters 12-hours post-dose Ventricular rate (bpm) |
| Spirometry Change From Baseline | 12 hours | Change from baseline for spirometery measures 12-hours post-dose |
| Serum Potassium Change From Baseline | 12 hours | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Australia
Participant flow
Recruitment details
Conducted at a single site in Australia from May 2009 through July 2009. Study participation was a maximum of 7 weeks.
Pre-assignment details
Study evaluating a single administration of inhaled treatment (PT001, PT003, PT005 and PT001+PT005 delivered from separate inhalers as a loose combination).Each subject was randomized to 1 of 4 sequences. Each sequence included the four treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Any treatment arm | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 3 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 27.4 Years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 15 | 6 / 13 | 8 / 16 | 9 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 13 | 0 / 16 | 0 / 15 |
Outcome results
Primary
Blood Chemistry Change From Baseline
Series of 11 blood chemistries assessed throughout the study
Time frame: 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects
Population: All patients in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo + PT001 | Blood Chemistry Change From Baseline | Sodium | 0.76 mmol/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | Chloride | -1.29 mmol/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | Urea | 0.12 mmol/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | Calcium | -0.01 mmol/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | Bicarbonate | 0.64 mmol/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | Glucose | -0.17 mmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Glucose | -0.34 mmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Calcium | -0.04 mmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Sodium | 0.78 mmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Urea | -0.05 mmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Chloride | -0.4 mmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Bicarbonate | 0.05 mmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Chloride | -0.75 mmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Urea | -0.11 mmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Calcium | -0.03 mmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Glucose | -0.34 mmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Bicarbonate | 0.44 mmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Sodium | 0.35 mmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Bicarbonate | 0.47 mmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Glucose | 0.45 mmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Chloride | -1.2 mmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Calcium | -0.01 mmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Sodium | 0.6 mmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Urea | -0.33 mmol/L |
Primary
Blood Chemistry Change From Baseline
Series of 11 blood chemistries assessed throughout the study
Time frame: 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects
Population: All subjects in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo + PT001 | Blood Chemistry Change From Baseline | Creatinine | 2.19 µmol/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | Bilirubin | -1.4 µmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Bilirubin | -2.18 µmol/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | Creatinine | 1.45 µmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Creatinine | 0.44 µmol/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | Bilirubin | -2.32 µmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Creatinine | -0.8 µmol/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | Bilirubin | -2.07 µmol/L |
Primary
Blood Chemistry Change From Baseline
Series of 11 blood chemistries assessed throughout the study
Time frame: 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects
Population: All patients in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo + PT001 | Blood Chemistry Change From Baseline | AST | -0.83 U/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | ALP | 2.99 U/L |
| Placebo + PT001 | Blood Chemistry Change From Baseline | ALT | 0.07 U/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | AST | 0.25 U/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | ALP | 3.59 U/L |
| Placebo + PT005 | Blood Chemistry Change From Baseline | ALT | -1.21 U/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | ALP | 1.39 U/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | ALT | -0.41 U/L |
| PT001 + PT005 | Blood Chemistry Change From Baseline | AST | -2.91 U/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | ALP | 2 U/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | AST | -1.67 U/L |
| Placebo + PT003 | Blood Chemistry Change From Baseline | ALT | -0.33 U/L |
Primary
ECG Change From Baseline
Change from baseline for ECG parameters 12-hours post-dose Ventricular rate (bpm)
Time frame: 12 hours
Population: Safety population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | ECG Change From Baseline | 1.5 bpm |
| Placebo + PT005 | ECG Change From Baseline | 4.7 bpm |
| PT001 + PT005 | ECG Change From Baseline | 5.2 bpm |
| Placebo + PT003 | ECG Change From Baseline | 4.0 bpm |
Primary
ECG Change From Baseline
Change from baseline for ECG parameters 12-hours post-dose
Time frame: 12 hours
Population: Safety population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo + PT001 | ECG Change From Baseline | QTcB (ms) | -3.7 ms |
| Placebo + PT001 | ECG Change From Baseline | QRS duration (ms) | -3.0 ms |
| Placebo + PT001 | ECG Change From Baseline | QTcF (ms) | -5.1 ms |
| Placebo + PT001 | ECG Change From Baseline | QT interval (ms) | -8.6 ms |
| Placebo + PT001 | ECG Change From Baseline | PR interval (ms) | -11.0 ms |
| Placebo + PT005 | ECG Change From Baseline | QT interval (ms) | -9.4 ms |
| Placebo + PT005 | ECG Change From Baseline | QTcB (ms) | 5.3 ms |
| Placebo + PT005 | ECG Change From Baseline | QTcF (ms) | 0.0 ms |
| Placebo + PT005 | ECG Change From Baseline | QRS duration (ms) | -5.4 ms |
| Placebo + PT005 | ECG Change From Baseline | PR interval (ms) | -8.3 ms |
| PT001 + PT005 | ECG Change From Baseline | QT interval (ms) | -10.1 ms |
| PT001 + PT005 | ECG Change From Baseline | PR interval (ms) | -5.3 ms |
| PT001 + PT005 | ECG Change From Baseline | QRS duration (ms) | 0.4 ms |
| PT001 + PT005 | ECG Change From Baseline | QTcB (ms) | 5.4 ms |
| PT001 + PT005 | ECG Change From Baseline | QTcF (ms) | -0.1 ms |
| Placebo + PT003 | ECG Change From Baseline | QTcB (ms) | -2.1 ms |
| Placebo + PT003 | ECG Change From Baseline | QRS duration (ms) | -2.0 ms |
| Placebo + PT003 | ECG Change From Baseline | PR interval (ms) | -10.4 ms |
| Placebo + PT003 | ECG Change From Baseline | QT interval (ms) | -12.8 ms |
| Placebo + PT003 | ECG Change From Baseline | QTcF (ms) | -5.9 ms |
Primary
Heart Rate Change From Baseline
Change from baseline for heart rate 12-hours post-dose Heart rate (bpm)
Time frame: 12 hours
Population: All subjects in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | Heart Rate Change From Baseline | 2.0 bpm |
| Placebo + PT005 | Heart Rate Change From Baseline | 4.4 bpm |
| PT001 + PT005 | Heart Rate Change From Baseline | 2.9 bpm |
| Placebo + PT003 | Heart Rate Change From Baseline | 1.8 bpm |
Primary
Hematology Change From Baseline
Hematology assessments taken throughout the study Hematocrit
Time frame: 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects
Population: All subjects in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | Hematology Change From Baseline | 0.01 % of Red Blood Cells in the blood |
| Placebo + PT005 | Hematology Change From Baseline | 0.01 % of Red Blood Cells in the blood |
| PT001 + PT005 | Hematology Change From Baseline | 0.01 % of Red Blood Cells in the blood |
| Placebo + PT003 | Hematology Change From Baseline | 0.01 % of Red Blood Cells in the blood |
Primary
Hematology Change From Baseline
Hematology assessments taken throughout the study
Time frame: 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects
Population: All subjects in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo + PT001 | Hematology Change From Baseline | WCC | 17.93 (10^9 cells/L) |
| Placebo + PT001 | Hematology Change From Baseline | Platelets | 1.08 (10^9 cells/L) |
| Placebo + PT005 | Hematology Change From Baseline | Platelets | 0.88 (10^9 cells/L) |
| Placebo + PT005 | Hematology Change From Baseline | WCC | 20.61 (10^9 cells/L) |
| PT001 + PT005 | Hematology Change From Baseline | WCC | 10.8 (10^9 cells/L) |
| PT001 + PT005 | Hematology Change From Baseline | Platelets | 0.93 (10^9 cells/L) |
| Placebo + PT003 | Hematology Change From Baseline | WCC | 20.33 (10^9 cells/L) |
| Placebo + PT003 | Hematology Change From Baseline | Platelets | 0.67 (10^9 cells/L) |
Primary
Hematology Change From Baseline
Hematology assessments taken throughout the study Hemoglobin
Time frame: 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects
Population: All subjects in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | Hematology Change From Baseline | 2.45 g/L |
| Placebo + PT005 | Hematology Change From Baseline | 2.95 g/L |
| PT001 + PT005 | Hematology Change From Baseline | 1.73 g/L |
| Placebo + PT003 | Hematology Change From Baseline | 3.33 g/L |
Primary
Serum Potassium Change From Baseline
Time frame: 12 hours
Population: All subjects in the Safety Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + PT001 | Serum Potassium Change From Baseline | 4.4 mmol/L |
| Placebo + PT005 | Serum Potassium Change From Baseline | 4.1 mmol/L |
| PT001 + PT005 | Serum Potassium Change From Baseline | 4.1 mmol/L |
| Placebo + PT003 | Serum Potassium Change From Baseline | 4.2 mmol/L |
Primary
Spirometry Change From Baseline
Change from baseline for spirometery measures 12-hours post-dose FEV/FVC (%)
Time frame: 12 hours
Population: Safety population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | Spirometry Change From Baseline | 3.0 Ratio |
| Placebo + PT005 | Spirometry Change From Baseline | 3.4 Ratio |
| PT001 + PT005 | Spirometry Change From Baseline | 3.2 Ratio |
| Placebo + PT003 | Spirometry Change From Baseline | 3.6 Ratio |
Primary
Spirometry Change From Baseline
Change from baseline for spirometery measures 12-hours post-dose
Time frame: 12 hours
Population: Safety population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo + PT001 | Spirometry Change From Baseline | FEV1 (L) | 0.260 Liters |
| Placebo + PT001 | Spirometry Change From Baseline | FVC (L) | 0.145 Liters |
| Placebo + PT005 | Spirometry Change From Baseline | FVC (L) | 0.0 Liters |
| Placebo + PT005 | Spirometry Change From Baseline | FEV1 (L) | 0.148 Liters |
| PT001 + PT005 | Spirometry Change From Baseline | FEV1 (L) | 0.202 Liters |
| PT001 + PT005 | Spirometry Change From Baseline | FVC (L) | 0.082 Liters |
| Placebo + PT003 | Spirometry Change From Baseline | FEV1 (L) | 0.195 Liters |
| Placebo + PT003 | Spirometry Change From Baseline | FVC (L) | 0.045 Liters |
Primary
Spirometry Change From Baseline
Change from baseline for spirometery measures 12-hours post-dose (FEV1 % predicted)
Time frame: 12 hours
Population: Safety population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | Spirometry Change From Baseline | 7.2 % predicted |
| Placebo + PT005 | Spirometry Change From Baseline | 4.5 % predicted |
| PT001 + PT005 | Spirometry Change From Baseline | 5.2 % predicted |
| Placebo + PT003 | Spirometry Change From Baseline | 5.0 % predicted |
Primary
Spirometry Change From Baseline
Change from baseline for spirometery measures 12-hours post-dose PEFR (L/min)
Time frame: 12 hours
Population: Safety population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | Spirometry Change From Baseline | 40.4 L/min |
| Placebo + PT005 | Spirometry Change From Baseline | 32.1 L/min |
| PT001 + PT005 | Spirometry Change From Baseline | 40.1 L/min |
| Placebo + PT003 | Spirometry Change From Baseline | 31.6 L/min |
Primary
Symptoms of Dry Mouth
Number of participants reporting dry mouth at 12 hours post-dose
Time frame: 12 hours
Population: All subjects in the Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + PT001 | Symptoms of Dry Mouth | 30 minutes post-dose | 4 Participants |
| Placebo + PT001 | Symptoms of Dry Mouth | 1-hour post-dose | 3 Participants |
| Placebo + PT001 | Symptoms of Dry Mouth | 6-hours post-dose | 1 Participants |
| Placebo + PT001 | Symptoms of Dry Mouth | 4-hours post-dose | 1 Participants |
| Placebo + PT001 | Symptoms of Dry Mouth | 12-hours post-dose | 1 Participants |
| Placebo + PT001 | Symptoms of Dry Mouth | 2-hours post-dose | 3 Participants |
| Placebo + PT001 | Symptoms of Dry Mouth | 8-hours post-dose | 1 Participants |
| Placebo + PT001 | Symptoms of Dry Mouth | Immediately pre-dose | 3 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | 12-hours post-dose | 1 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | 4-hours post-dose | 1 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | 6-hours post-dose | 1 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | 30 minutes post-dose | 3 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | Immediately pre-dose | 1 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | 1-hour post-dose | 2 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | 8-hours post-dose | 1 Participants |
| Placebo + PT005 | Symptoms of Dry Mouth | 2-hours post-dose | 1 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | 6-hours post-dose | 2 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | 8-hours post-dose | 2 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | 30 minutes post-dose | 4 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | 12-hours post-dose | 2 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | 1-hour post-dose | 3 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | Immediately pre-dose | 3 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | 2-hours post-dose | 3 Participants |
| PT001 + PT005 | Symptoms of Dry Mouth | 4-hours post-dose | 3 Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | 12-hours post-dose | NA Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | Immediately pre-dose | 1 Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | 30 minutes post-dose | 5 Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | 1-hour post-dose | 3 Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | 2-hours post-dose | 1 Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | 4-hours post-dose | 0 Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | 6-hours post-dose | NA Participants |
| Placebo + PT003 | Symptoms of Dry Mouth | 8-hours post-dose | NA Participants |
Primary
Symptoms of Tremor
Number of participants reporting tremor at 12 hours post-dose
Time frame: 12 hours
Population: All subjects in the Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + PT001 | Symptoms of Tremor | Immediately pre-dose | 0 Participants |
| Placebo + PT001 | Symptoms of Tremor | 30-minutes post-dose | 0 Participants |
| Placebo + PT001 | Symptoms of Tremor | 1-hour post-dose | 0 Participants |
| Placebo + PT001 | Symptoms of Tremor | 2-hours post-dose | 0 Participants |
| Placebo + PT001 | Symptoms of Tremor | 4-hours post-dose | NA Participants |
| Placebo + PT001 | Symptoms of Tremor | 6-hours post-dose | NA Participants |
| Placebo + PT001 | Symptoms of Tremor | 8-hours post-dose | NA Participants |
| Placebo + PT001 | Symptoms of Tremor | 12-hours post-dose | NA Participants |
| Placebo + PT005 | Symptoms of Tremor | 6-hours post-dose | 0 Participants |
| Placebo + PT005 | Symptoms of Tremor | 4-hours post-dose | 1 Participants |
| Placebo + PT005 | Symptoms of Tremor | 30-minutes post-dose | 0 Participants |
| Placebo + PT005 | Symptoms of Tremor | 12-hours post-dose | NA Participants |
| Placebo + PT005 | Symptoms of Tremor | 8-hours post-dose | NA Participants |
| Placebo + PT005 | Symptoms of Tremor | 2-hours post-dose | 0 Participants |
| Placebo + PT005 | Symptoms of Tremor | 1-hour post-dose | 0 Participants |
| Placebo + PT005 | Symptoms of Tremor | Immediately pre-dose | 0 Participants |
| PT001 + PT005 | Symptoms of Tremor | 8-hours post-dose | NA Participants |
| PT001 + PT005 | Symptoms of Tremor | 1-hour post-dose | 0 Participants |
| PT001 + PT005 | Symptoms of Tremor | 2-hours post-dose | 1 Participants |
| PT001 + PT005 | Symptoms of Tremor | 4-hours post-dose | 1 Participants |
| PT001 + PT005 | Symptoms of Tremor | 6-hours post-dose | 0 Participants |
| PT001 + PT005 | Symptoms of Tremor | 12-hours post-dose | NA Participants |
| PT001 + PT005 | Symptoms of Tremor | Immediately pre-dose | 0 Participants |
| PT001 + PT005 | Symptoms of Tremor | 30-minutes post-dose | 0 Participants |
| Placebo + PT003 | Symptoms of Tremor | 1-hour post-dose | 0 Participants |
| Placebo + PT003 | Symptoms of Tremor | 2-hours post-dose | 0 Participants |
| Placebo + PT003 | Symptoms of Tremor | 30-minutes post-dose | 0 Participants |
| Placebo + PT003 | Symptoms of Tremor | Immediately pre-dose | 0 Participants |
| Placebo + PT003 | Symptoms of Tremor | 4-hours post-dose | NA Participants |
| Placebo + PT003 | Symptoms of Tremor | 12-hours post-dose | NA Participants |
| Placebo + PT003 | Symptoms of Tremor | 8-hours post-dose | NA Participants |
| Placebo + PT003 | Symptoms of Tremor | 6-hours post-dose | NA Participants |
Primary
Vital Sign Change Baseline; Blood Pressure
Vital sign change baseline; blood pressure
Time frame: 12 hours
Population: All subjects in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo + PT001 | Vital Sign Change Baseline; Blood Pressure | Systolic blood pressure (mmHg) | 3.3 mmHg |
| Placebo + PT001 | Vital Sign Change Baseline; Blood Pressure | Diastolic blood pressure (mmHg) | 6.3 mmHg |
| Placebo + PT005 | Vital Sign Change Baseline; Blood Pressure | Diastolic blood pressure (mmHg) | 1.5 mmHg |
| Placebo + PT005 | Vital Sign Change Baseline; Blood Pressure | Systolic blood pressure (mmHg) | 1.0 mmHg |
| PT001 + PT005 | Vital Sign Change Baseline; Blood Pressure | Systolic blood pressure (mmHg) | 0.1 mmHg |
| PT001 + PT005 | Vital Sign Change Baseline; Blood Pressure | Diastolic blood pressure (mmHg) | 0.6 mmHg |
| Placebo + PT003 | Vital Sign Change Baseline; Blood Pressure | Systolic blood pressure (mmHg) | 0.4 mmHg |
| Placebo + PT003 | Vital Sign Change Baseline; Blood Pressure | Diastolic blood pressure (mmHg) | 1.6 mmHg |
Primary
Vital Sign Change From Baseline, SpO2
Vital Sign Change from baseline 12-hours post-dose SpO2 (%)
Time frame: 12 hours
Population: All subjects in the Safety Population that had a valid measurement for the parameter
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + PT001 | Vital Sign Change From Baseline, SpO2 | 0.2 % blood oxygen saturation level |
| Placebo + PT005 | Vital Sign Change From Baseline, SpO2 | 0.1 % blood oxygen saturation level |
| PT001 + PT005 | Vital Sign Change From Baseline, SpO2 | -0.1 % blood oxygen saturation level |
| Placebo + PT003 | Vital Sign Change From Baseline, SpO2 | 0.1 % blood oxygen saturation level |
Secondary
Plasma Formoterol PK Parameters
Various pharmacokinetic parameters for plasma formoterol
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + PT001 | Plasma Formoterol PK Parameters | AUC0-tlast (h*pg/mL) | 47.9 h*pg/mL | Standard Deviation 12.3 |
| Placebo + PT001 | Plasma Formoterol PK Parameters | AUC0-12 (h*pg/mL) | 48.1 h*pg/mL | Standard Deviation 12.2 |
| Placebo + PT005 | Plasma Formoterol PK Parameters | AUC0-tlast (h*pg/mL) | 61.2 h*pg/mL | Standard Deviation 16.5 |
| Placebo + PT005 | Plasma Formoterol PK Parameters | AUC0-12 (h*pg/mL) | 61.2 h*pg/mL | Standard Deviation 16.6 |
| PT001 + PT005 | Plasma Formoterol PK Parameters | AUC0-tlast (h*pg/mL) | 57.9 h*pg/mL | Standard Deviation 16.3 |
| PT001 + PT005 | Plasma Formoterol PK Parameters | AUC0-12 (h*pg/mL) | 57.8 h*pg/mL | Standard Deviation 16.2 |
Secondary
Plasma Formoterol PK Parameters AUC0-inf (h*pg/mL)
Various pharmacokinetic parameters for plasma formoterol
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Formoterol PK Parameters AUC0-inf (h*pg/mL) | 56.1 h*pg/mL | Standard Deviation 8.3 |
| Placebo + PT005 | Plasma Formoterol PK Parameters AUC0-inf (h*pg/mL) | 76.4 h*pg/mL | Standard Deviation 18.5 |
| PT001 + PT005 | Plasma Formoterol PK Parameters AUC0-inf (h*pg/mL) | 67.0 h*pg/mL | Standard Deviation 12.8 |
Secondary
Plasma Formoterol PK Parameters (Cmax)
Pharmacokinetic parameters for plasma formoterol Cmax
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Formoterol PK Parameters (Cmax) | 10.4 pg/mL | Standard Deviation 3.8 |
| Placebo + PT005 | Plasma Formoterol PK Parameters (Cmax) | 13.2 pg/mL | Standard Deviation 4.5 |
| PT001 + PT005 | Plasma Formoterol PK Parameters (Cmax) | 11.9 pg/mL | Standard Deviation 4 |
Secondary
Plasma Formoterol PK Parameters (ke)
Pharmacokinetic parameters for plasma formoterol ke
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Formoterol PK Parameters (ke) | 0.142 1/h | Standard Deviation 0.035 |
| Placebo + PT005 | Plasma Formoterol PK Parameters (ke) | 0.135 1/h | Standard Deviation 0.025 |
| PT001 + PT005 | Plasma Formoterol PK Parameters (ke) | 0.126 1/h | Standard Deviation 0.032 |
Secondary
Plasma Formoterol PK Parameters (t1/2)
Various pharmacokinetic parameters for plasma formoterol
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Formoterol PK Parameters (t1/2) | 5.12 h | Standard Deviation 1.1 |
| Placebo + PT005 | Plasma Formoterol PK Parameters (t1/2) | 5.28 h | Standard Deviation 1.02 |
| PT001 + PT005 | Plasma Formoterol PK Parameters (t1/2) | 5.8 h | Standard Deviation 1.32 |
Secondary
Plasma Formoterol PK Parameters (Tmax)
Various pharmacokinetic parameters for plasma formoterol
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Formoterol PK Parameters (Tmax) | 0.28 h | Standard Deviation 0.31 |
| Placebo + PT005 | Plasma Formoterol PK Parameters (Tmax) | 0.27 h | Standard Deviation 0.59 |
| PT001 + PT005 | Plasma Formoterol PK Parameters (Tmax) | 0.43 h | Standard Deviation 0.46 |
Secondary
Plasma Glycopyrrolate PK Parameters
Various pharmacokinetic parameters for plasma glycopyrrolate
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + PT001 | Plasma Glycopyrrolate PK Parameters | AUC0-tlast (h*pg/mL) | 156.6 h*pg/mL | Standard Deviation 76.7 |
| Placebo + PT001 | Plasma Glycopyrrolate PK Parameters | AUC0-12 (h*pg/mL) | 156.7 h*pg/mL | Standard Deviation 76.5 |
| Placebo + PT005 | Plasma Glycopyrrolate PK Parameters | AUC0-tlast (h*pg/mL) | 100.1 h*pg/mL | Standard Deviation 43.1 |
| Placebo + PT005 | Plasma Glycopyrrolate PK Parameters | AUC0-12 (h*pg/mL) | 100.6 h*pg/mL | Standard Deviation 42.4 |
| PT001 + PT005 | Plasma Glycopyrrolate PK Parameters | AUC0-tlast (h*pg/mL) | 78.4 h*pg/mL | Standard Deviation 36.2 |
| PT001 + PT005 | Plasma Glycopyrrolate PK Parameters | AUC0-12 (h*pg/mL) | 80.1 h*pg/mL | Standard Deviation 34.9 |
Secondary
Plasma Glycopyrrolate PK Parameters AUC0-inf (h*pg/mL)
Various pharmacokinetic parameters for plasma glycopyrrolate
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Glycopyrrolate PK Parameters AUC0-inf (h*pg/mL) | 172.4 h*pg/mL | Standard Deviation 88.6 |
| Placebo + PT005 | Plasma Glycopyrrolate PK Parameters AUC0-inf (h*pg/mL) | 137.2 h*pg/mL | Standard Deviation 55.4 |
| PT001 + PT005 | Plasma Glycopyrrolate PK Parameters AUC0-inf (h*pg/mL) | 100.8 h*pg/mL | Standard Deviation 50.5 |
Secondary
Plasma Glycopyrrolate PK Parameters Cmax (pg/mL)
Various pharmacokinetic parameters for plasma glycopyrrolate
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Glycopyrrolate PK Parameters Cmax (pg/mL) | 61.3 pg/mL | Standard Deviation 40.9 |
| Placebo + PT005 | Plasma Glycopyrrolate PK Parameters Cmax (pg/mL) | 77.8 pg/mL | Standard Deviation 72 |
| PT001 + PT005 | Plasma Glycopyrrolate PK Parameters Cmax (pg/mL) | 44.4 pg/mL | Standard Deviation 18.3 |
Secondary
Plasma Glycopyrrolate PK Parameters (ke)
Various pharmacokinetic parameters for plasma glycopyrrolate
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Glycopyrrolate PK Parameters (ke) | 0.143 1/h | Standard Deviation 0.047 |
| Placebo + PT005 | Plasma Glycopyrrolate PK Parameters (ke) | 0.147 1/h | Standard Deviation 0.042 |
| PT001 + PT005 | Plasma Glycopyrrolate PK Parameters (ke) | 0.155 1/h | Standard Deviation 0.059 |
Secondary
Plasma Glycopyrrolate PK Parameters (t1/2)
Various pharmacokinetic parameters for plasma glycopyrrolate
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Glycopyrrolate PK Parameters (t1/2) | 5.34 h | Standard Deviation 1.78 |
| Placebo + PT005 | Plasma Glycopyrrolate PK Parameters (t1/2) | 5.12 h | Standard Deviation 1.61 |
| PT001 + PT005 | Plasma Glycopyrrolate PK Parameters (t1/2) | 5.12 h | Standard Deviation 2.07 |
Secondary
Plasma Glycopyrrolate PK Parameters (Tmax)
Various pharmacokinetic parameters for plasma glycopyrrolate
Time frame: 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
Population: Subjects with an evaluable profile for this analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + PT001 | Plasma Glycopyrrolate PK Parameters (Tmax) | 0.16 h | Standard Deviation 0.14 |
| Placebo + PT005 | Plasma Glycopyrrolate PK Parameters (Tmax) | 0.07 h | Standard Deviation 0.06 |
| PT001 + PT005 | Plasma Glycopyrrolate PK Parameters (Tmax) | 0.06 h | Standard Deviation 0.03 |