Safety Issues
Conditions
Brief summary
This is a phase 1A randomized double blind placebo controlled single ascending dose and multiple ascending dose trial of inhaled PK10571 (GB002) in healthy adult subjects.
Detailed description
This is a first-in-human, single-center, randomized, double-blind, placebo-controlled, two-part study in healthy adult males and females of non-childbearing potential. Double-Blind means neither the study subject nor the investigator knows if PK10571 or placebo is being given. Placebo means a capsule filled with a powder that does not contain the active drug, PK10571. Because the safety profile of PK10571 in humans is unknown and this is the first clinical study to assess PK10571 in humans, a single-ascending dose design will be used in Part A of the study going from a low dose to higher doses based on safety. Part B will be a multiple-ascending dose design to be run only after review of safety and measurement of drug levels in the blood from Part A. In the single ascending dose study (Part A) up to five doses may be given to different groups of study subjects based on safety and measurement of drug levels in the blood. Subjects will be randomized into one dose cohort to receive either PK10571 or placebo. Within each cohort, 6 subjects will receive active drug and 2 subjects will receive placebo. In the multiple ascending dose study (Part B), up to three doses of PK10571 will be tested. The daily dose will be administered daily for 7 days with close clinical monitoring. The dose for the first cohort of Part B will be determined by review of the safety and drug levels from Part A by the Safety Review Committee. The dose interval for the first cohort of Part B (i.e., once daily, twice daily, or up to three times daily) will be determined by review of the safety and drug levels in the blood from Part A by the Safety Review committee. Subsequent doses and dosing intervals will be determined by review of the safety and drug levels from the prior cohort.
Interventions
DRUGGB002
Inhaled GB002
dry powder inhaler used for inhalation of active drug or placebo
DRUGPlacebo
Inhaled placebo
Sponsors
Pulmokine Inc.
Worldwide Clinical Trials
GB002, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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
* Males and females (if unable to become pregnant) * Age 18-55 * Body mass index (BMI) 18-32 kg/m\^2 and minimum weight of 50 kg (110 lbs) * Non-smoker * Ability to give informed consent * Ability to remain in study unit for duration of study and return for outpatient visits * Ability to use dry powder inhaler (DPI) effectively (See full protocol for additional details.)
Exclusion criteria
* Hospitalization within the 6 months prior to the first dose of study treatment * History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results * History or presence of active lung disease (i.e., asthma, chronic obstructive pulmonary disease \[COPD\], pulmonary fibrosis, hemoptysis, bronchiectasis) or prior intubation * Currently uses an inhaler * History or presence of heart disease (i.e., prior myocardial infarction \[MI\], coronary artery disease, heart failure, hypertension, pulmonary hypertension, valve disease, atrial fibrillation, other arrhythmia, or prolonged QT syndrome) * History or presence of cancer (with the exception of basal cell skin cancer that has been effectively treated) * History of diabetes mellitus * History of thyroid disease other than hypothyroidism control with levothyroxine and documented normal thyroid-stimulating hormone (TSH) * History of tuberculosis, Lyme disease, or other chronic or opportunistic infection. * History of positive purified protein derivative (PPD) skin test, or positive PPD test at screening * Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) at screening or has been previously treated for hepatitis B, hepatitis C, or HIV infection * History of smoking within the past 15 years * Is a female with a positive pregnancy test result, or who has the ability to become pregnant, or who is lactating * Has forced expiratory volume in 1 second (FEV1) less than 80% predicted, forced vital capacity (FVC) ˂80% predicted, or resting oxygen saturation less than 97% on room air at screening or baseline * Upper respiratory infection within the 3 months prior to the first dose of medication * History of major bleeding or major surgical procedure of any type within 6 months prior to the first dose of medication * History of minor bleeding disorders such as epistaxis, rectal bleeding (spots of blood on toilet paper), and gingival bleeding within 3 months before the study treatment * History of bleeding disorder or coagulopathy * Females with history of dysfunctional uterine bleeding, including history of menorrhagia or metrorrhagia, unless subject has had a hysterectomy. * History of GI bleed * Has used any over-the-counter (OTC) medication, nutritional or dietary supplements, herbal preparations, or vitamins within 7 days prior to the first dose of medication * Has used any antiplatelet agents such as acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel (or similar agent) or anti-coagulants within 7 days prior to the first dose of medication * Has used any prescription medication, except female hormonal replacement therapy, within 14 days prior to the first dose of study medication * Has been treated with any known drugs that are moderate or strong inhibitors/inducers of CYP enzymes such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication and that in the Investigator's judgment may impact subject safety or the validity of the study results * History of peripheral vascular disease * History of autoimmune or collagen vascular disease * History of sleep apnea * History of clinically significant allergy to medications * History of anaphylaxis * History of liver disease * History of alcohol or drug abuse * Prolonged QTc on 12-lead ECG (i.e., QTc corrected using Fridericia's formula \[QTcF\] ˃450 msec), PR \>210 msec, or QRS \>110 msec at screening. * Evidence of prior MI on ECG; presence of atrial fibrillation on ECG; presence of pre-excitation, 2nd or 3rd degree heart block, or abnormal waveform morphology that would preclude accurate measurement of the QT interval duration or other clinically significant abnormalities * Chest x-ray reveals presence of infiltrate or other abnormality (mass, granuloma, fibrosis, pulmonary thickening, pleural effusion, pulmonary edema, wide mediastinum, cardiomegaly, or clinically significant increased interstitial markings) * History of neurologic disorder (i.e., multiple sclerosis, amyotrophic lateral sclerosis \[ALS\], cerebrovascular accident \[CVA\], transient ischemic attach \[TIA\]) * History of deep vein thrombosis or pulmonary embolus * History of clotting disorder * History of mental illness requiring drug treatment or hospitalization * History of renal failure or proteinuria (defined as 1+ proteinuria: ≥75 mg/dL on isolated urinalysis) * Test results greater than the upper limit of normal (ULN) for AST, ALT, or total bilirubin * Out of range results on the following coagulation tests: INR, prothrombin time (PT), or partial thromboplastin time (PTT) * Total cholesterol \>250 mg/dL or triglycerides \>300 mg/dL at screening (based on fasting lipid profile) * Estimated creatinine clearance less than 60 mL/min * Hemoglobin at screening of \<11.5 g/dl (if female subject) or \<12.5 g/dl (if male subject) * Has a clinically significant abnormal finding on the physical exam, medical history, electrocardiogram (ECG), or clinical laboratory results at screening. Note: Subjects with abnormal laboratory results not specifically excluded by this protocol may be enrolled if the Investigator deems the out-of-range values as not clinically significant * History of treatment with a kinase inhibitor * Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication * Has donated blood or plasma within 30 days prior to the first dose of study medication * Has participated in another clinical trial (randomized subjects only) within 30 days prior to the first dose of study medication * Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates) or cotinine * Vital signs (measured sitting after 3 minutes rest) at screening that are not within the following ranges (inclusive): heart rate: 40-100 beats per minute \[bpm\]; systolic blood pressure (BP): 90-145 mmHg; diastolic BP: 50-95 mmHg. Out-of-range vital signs may be repeated once. Blood pressure will be measured in both arms at screening, with a 3-minute rest between each measurement. Predose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) prior to study drug administration. The Principal Investigator or designee will verify the eligibility of each subject with out-of-range vital signs and document approval prior to dosing * Significant difference (i.e., greater than 15 mmHg) between the systolic blood pressure in each arm at screening * History of lactose intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Analysis of Inhaled GB002: Vz/F, MAD | Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Rac for AUC0-24, MAD | Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Rac for Ctrough, MAD | Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: t1/2, MAD | Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance at Steady-State (CLss/F), MAD | Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days | An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A serious AE (SAE) is one that, in the view of either the investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. A TEAE is defined as any AE that has an onset on or after the first dose of study drug and before the end of study/end of treatment (EoS/ET) visit, or any pre-existing condition that has worsened in severity on or after the first dose of study drug and before the EoS/ET visit. |
| Number of Participants With Vital Sign Findings Reported as TEAEs | SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days | Vital signs evaluated included blood pressure, pulse oximetry, respiratory rate, and temperature. |
| Number of Participants With Clinically Significant Findings in Physical Examinations | SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days | Physical examination assessments included: physical exam for general appearance; head, ears, eyes, nose and throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities, musculoskeletal and neurological. |
| Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | SAD: Baseline, Day 2, 24 hours; MAD: Baseline, Day 8, 24 hours | 12-lead electrocardiograms (ECG) assessments included heart rate, PR interval, QRS duration, QT interval, QTc interval, QTc interval corrected using Bazett's formula (QTcB), QTc interval corrected using Fridericia's formula (QTcF), RR interval. |
| Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days | Pulmonary function tests included forced vital capacity; forced expiratory volume in 1 second (FEV1); forced expiratory flow 25%-75% (FEF25-75); percent predicted forced vital capacity; percent predicted FEV1; and percent predicted FEF25-75. |
| Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD | 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD | 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD | 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD | 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD | 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD | 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | CL/F is based on nominal (scheduled) dose. |
| PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD | 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | Vz/F is based on nominal (scheduled) dose. |
| PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD | Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD | Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD | Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD | Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
| PK Analysis of Inhaled GB002: Accumulation Ratio (Rac) for Cmax After Dose 1, MAD | Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin | SAD: from baseline to 11 days, MAD: from baseline to 35 days | Measurement of hemoglobin |
| Change From Baseline in Kidney Function Parameters | SAD: from baseline to 11 days, MAD: from baseline to 35 days | Measurement of blood urea nitrogen (BUN) and creatinine. |
| Change From Baseline in Liver Function Parameters | SAD: from baseline to 11 days, MAD: from baseline to 35 days | Measurement of liver function (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]). |
| Change From Baseline in White Blood Cell Count | SAD: from baseline to 11 days, MAD: from baseline to 35 days | Measurement of white blood cell count |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SAD GB002 Placebo QD A placebo SAD inhaled QD over 11 days in healthy volunteers | 10 |
| SAD GB002 3.75 mg QD GB002 SAD 3.75 mg inhaled QD over 11 days in healthy volunteers | 6 |
| SAD GB002 7.5 mg QD GB002 SAD 7.5 mg inhaled QD over 11 days in healthy volunteers | 6 |
| SAD GB002 15 mg QD GB002 SAD 15 mg inhaled QD over 11 days in healthy volunteers | 6 |
| SAD GB002 30 mg QD GB002 SAD 30 mg inhaled QD over 11 days in healthy volunteers | 6 |
| SAD GB002 48 mg QD GB002 SAD 48 mg inhaled QD over 11 days in healthy volunteers | 7 |
| MAD GB002 Placebo BID/TID A placebo MAD inhaled either BID or TID over 35 days in healthy volunteers | 6 |
| MAD GB002 18 mg BID GB002 MAD 18 mg inhaled BID over 35 days in healthy volunteers | 6 |
| MAD GB002 24 mg TID GB002 MAD 24 mg inhaled TID over 35 days in healthy volunteers | 7 |
| MAD GB002 48 mg TID GB002 MAD 48 mg inhaled TID over 35 days in healthy volunteers | 6 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | SAD GB002 Placebo QD | SAD GB002 3.75 mg QD | SAD GB002 7.5 mg QD | SAD GB002 15 mg QD | SAD GB002 30 mg QD | SAD GB002 48 mg QD | MAD GB002 Placebo BID/TID | MAD GB002 18 mg BID | MAD GB002 24 mg TID | MAD GB002 48 mg TID | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 7.72 | 39.0 years STANDARD_DEVIATION 7.54 | 36.8 years STANDARD_DEVIATION 10.34 | 38.5 years STANDARD_DEVIATION 8.78 | 39.5 years STANDARD_DEVIATION 6.28 | 35.4 years STANDARD_DEVIATION 9.59 | 33.3 years STANDARD_DEVIATION 11.31 | 49.3 years STANDARD_DEVIATION 4.13 | 31.7 years STANDARD_DEVIATION 8.83 | 41.0 years STANDARD_DEVIATION 6.1 | 38.8 years STANDARD_DEVIATION 9.06 |
| BMI | 26.85 kg/m^2 STANDARD_DEVIATION 2.804 | 28.07 kg/m^2 STANDARD_DEVIATION 3.195 | 23.88 kg/m^2 STANDARD_DEVIATION 3.407 | 26.60 kg/m^2 STANDARD_DEVIATION 1.932 | 30.18 kg/m^2 STANDARD_DEVIATION 1.52 | 25.86 kg/m^2 STANDARD_DEVIATION 3.574 | 28.25 kg/m^2 STANDARD_DEVIATION 3.384 | 28.18 kg/m^2 STANDARD_DEVIATION 2.712 | 26.89 kg/m^2 STANDARD_DEVIATION 3.609 | 23.20 kg/m^2 STANDARD_DEVIATION 2.589 | 26.79 kg/m^2 STANDARD_DEVIATION 3.352 |
| Bodyweight | 79.55 kg STANDARD_DEVIATION 8.023 | 77.77 kg STANDARD_DEVIATION 15.075 | 70.37 kg STANDARD_DEVIATION 16.17 | 76.33 kg STANDARD_DEVIATION 8.091 | 90.68 kg STANDARD_DEVIATION 18.925 | 70.37 kg STANDARD_DEVIATION 6.307 | 81.27 kg STANDARD_DEVIATION 15.944 | 74.58 kg STANDARD_DEVIATION 12.449 | 72.24 kg STANDARD_DEVIATION 8.247 | 65.45 kg STANDARD_DEVIATION 12.565 | 75.95 kg STANDARD_DEVIATION 13.255 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 3 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 172.52 cm STANDARD_DEVIATION 12.156 | 165.82 cm STANDARD_DEVIATION 10.699 | 171.03 cm STANDARD_DEVIATION 14.785 | 169.30 cm STANDARD_DEVIATION 6.427 | 172.58 cm STANDARD_DEVIATION 16.351 | 165.84 cm STANDARD_DEVIATION 11.783 | 169.22 cm STANDARD_DEVIATION 11.468 | 162.27 cm STANDARD_DEVIATION 8.19 | 164.43 cm STANDARD_DEVIATION 9.351 | 167.45 cm STANDARD_DEVIATION 10.418 | 168.23 cm STANDARD_DEVIATION 11.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 48 Participants |
| Region of Enrollment United States | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 66 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 32 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 0 / 10 | 0 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 1 / 7 | 2 / 6 | 1 / 6 | 5 / 7 | 4 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 |
Outcome results
Primary
Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests
Pulmonary function tests included forced vital capacity; forced expiratory volume in 1 second (FEV1); forced expiratory flow 25%-75% (FEF25-75); percent predicted forced vital capacity; percent predicted FEV1; and percent predicted FEF25-75.
Time frame: SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days
Population: Safety Population: all participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD GB002 Placebo QD | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| SAD GB002 15 mg QD | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| SAD GB002 48 mg QD | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| MAD GB002 18 mg BID | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| MAD GB002 24 mg TID | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
| MAD GB002 48 mg TID | Number of Participants With Clinically Significant Abnormal Findings in Pulmonary Function Tests | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation)
12-lead electrocardiograms (ECG) assessments included heart rate, PR interval, QRS duration, QT interval, QTc interval, QTc interval corrected using Bazett's formula (QTcB), QTc interval corrected using Fridericia's formula (QTcF), RR interval.
Time frame: SAD: Baseline, Day 2, 24 hours; MAD: Baseline, Day 8, 24 hours
Population: Safety Population: all participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD GB002 Placebo QD | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| SAD GB002 15 mg QD | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| SAD GB002 48 mg QD | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| MAD GB002 18 mg BID | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| MAD GB002 24 mg TID | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
| MAD GB002 48 mg TID | Number of Participants With Clinically Significant Changes From Baseline in ECG Data (Overall Interpretation) | 0 Participants |
Primary
Number of Participants With Clinically Significant Findings in Physical Examinations
Physical examination assessments included: physical exam for general appearance; head, ears, eyes, nose and throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities, musculoskeletal and neurological.
Time frame: SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days
Population: Safety Population: all participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD GB002 Placebo QD | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| SAD GB002 15 mg QD | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| SAD GB002 48 mg QD | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| MAD GB002 18 mg BID | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| MAD GB002 24 mg TID | Number of Participants With Clinically Significant Findings in Physical Examinations | 0 Participants |
| MAD GB002 48 mg TID | Number of Participants With Clinically Significant Findings in Physical Examinations | 1 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A serious AE (SAE) is one that, in the view of either the investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. A TEAE is defined as any AE that has an onset on or after the first dose of study drug and before the end of study/end of treatment (EoS/ET) visit, or any pre-existing condition that has worsened in severity on or after the first dose of study drug and before the EoS/ET visit.
Time frame: SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days
Population: Safety Population: all participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAD GB002 Placebo QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| SAD GB002 Placebo QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| SAD GB002 Placebo QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 0 Participants |
| SAD GB002 Placebo QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| SAD GB002 Placebo QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 2 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| SAD GB002 15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| SAD GB002 15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 1 Participants |
| SAD GB002 15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| SAD GB002 15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 1 Participants |
| SAD GB002 15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 2 Participants |
| SAD GB002 30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| SAD GB002 48 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| SAD GB002 48 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 1 Participants |
| SAD GB002 48 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 1 Participants |
| SAD GB002 48 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| SAD GB002 48 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 2 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 2 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| MAD GB002 18 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| MAD GB002 18 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 1 Participants |
| MAD GB002 18 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| MAD GB002 18 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 1 Participants |
| MAD GB002 18 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| MAD GB002 24 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 5 Participants |
| MAD GB002 24 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| MAD GB002 24 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 3 Participants |
| MAD GB002 24 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| MAD GB002 24 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| MAD GB002 48 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious Treatment Related TEAE | 0 Participants |
| MAD GB002 48 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| MAD GB002 48 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Early Termination | 0 Participants |
| MAD GB002 48 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment Related TEAE | 4 Participants |
| MAD GB002 48 mg TID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
Primary
Number of Participants With Vital Sign Findings Reported as TEAEs
Vital signs evaluated included blood pressure, pulse oximetry, respiratory rate, and temperature.
Time frame: SAD: from first dose of study drug to 11 days, MAD: from first dose of study drug to 35 days
Population: Safety Population: all participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD GB002 Placebo QD | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| SAD GB002 3.75 mg QD | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| SAD GB002 7.5 mg QD | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| SAD GB002 15 mg QD | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| SAD GB002 30 mg QD | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| SAD GB002 48 mg QD | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| MAD GB002 Placebo BID/TID | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| MAD GB002 18 mg BID | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
| MAD GB002 24 mg TID | Number of Participants With Vital Sign Findings Reported as TEAEs | 1 Participants |
| MAD GB002 48 mg TID | Number of Participants With Vital Sign Findings Reported as TEAEs | 0 Participants |
Primary
Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD
Time frame: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD | 19.4 ng/mL | Geometric Coefficient of Variation 41.32 |
| SAD GB002 3.75 mg QD | Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD | 51.7 ng/mL | Geometric Coefficient of Variation 36.88 |
| SAD GB002 7.5 mg QD | Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD | 161 ng/mL | Geometric Coefficient of Variation 33.12 |
| SAD GB002 15 mg QD | Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD | 184 ng/mL | Geometric Coefficient of Variation 78.39 |
| SAD GB002 30 mg QD | Pharmacokinetic (PK) Analysis of Inhaled GB002: Maximum Concentration (Cmax), SAD | 377 ng/mL | Geometric Coefficient of Variation 32.94 |
Primary
PK Analysis of Inhaled GB002: Accumulation Ratio (Rac) for Cmax After Dose 1, MAD
Time frame: Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Accumulation Ratio (Rac) for Cmax After Dose 1, MAD | 1.32 ratio | Geometric Coefficient of Variation 27.3 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Accumulation Ratio (Rac) for Cmax After Dose 1, MAD | 1.13 ratio | Geometric Coefficient of Variation 24.9 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Accumulation Ratio (Rac) for Cmax After Dose 1, MAD | 0.925 ratio | Geometric Coefficient of Variation 39.7 |
Primary
PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD
Time frame: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD | 3.48 hours | Geometric Coefficient of Variation 25.72 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD | 3.08 hours | Geometric Coefficient of Variation 28.54 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD | 3.32 hours | Geometric Coefficient of Variation 12.68 |
| SAD GB002 15 mg QD | PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD | 4.41 hours | Geometric Coefficient of Variation 23 |
| SAD GB002 30 mg QD | PK Analysis of Inhaled GB002: Apparent Terminal Elimination Half-Life (t1/2), SAD | 4.16 hours | Geometric Coefficient of Variation 20.35 |
Primary
PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance at Steady-State (CLss/F), MAD
Time frame: Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance at Steady-State (CLss/F), MAD | 77.9 L/h | Geometric Coefficient of Variation 13.55 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance at Steady-State (CLss/F), MAD | 87.1 L/h | Geometric Coefficient of Variation 20.17 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance at Steady-State (CLss/F), MAD | 76.9 L/h | Geometric Coefficient of Variation 42.25 |
Primary
PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD
CL/F is based on nominal (scheduled) dose.
Time frame: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD | 130 L/h | Geometric Coefficient of Variation 34.5 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD | 123 L/h | Geometric Coefficient of Variation 22.9 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD | 102 L/h | Geometric Coefficient of Variation 19.43 |
| SAD GB002 15 mg QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD | 140 L/h | Geometric Coefficient of Variation 28.48 |
| SAD GB002 30 mg QD | PK Analysis of Inhaled GB002: Apparent Total Plasma Clearance (CL/F), SAD | 113 L/h | Geometric Coefficient of Variation 44.41 |
Primary
PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD
Vz/F is based on nominal (scheduled) dose.
Time frame: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD | 650 L | Geometric Coefficient of Variation 25.86 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD | 548 L | Geometric Coefficient of Variation 24.12 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD | 489 L | Geometric Coefficient of Variation 18.33 |
| SAD GB002 15 mg QD | PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD | 889 L | Geometric Coefficient of Variation 32.24 |
| SAD GB002 30 mg QD | PK Analysis of Inhaled GB002: Apparent Volume of Distribution (Vz/F), SAD | 681 L | Geometric Coefficient of Variation 44.68 |
Primary
PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD
Time frame: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD | 28.9 h*ng/mL | Geometric Coefficient of Variation 34.5 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD | 60.9 h*ng/mL | Geometric Coefficient of Variation 22.9 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD | 147 h*ng/mL | Geometric Coefficient of Variation 19.43 |
| SAD GB002 15 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD | 215 h*ng/mL | Geometric Coefficient of Variation 28.48 |
| SAD GB002 30 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Infinity (AUCinf), SAD | 423 h*ng/mL | Geometric Coefficient of Variation 44.41 |
Primary
PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD
Time frame: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD | 28.7 h*ng/mL | Geometric Coefficient of Variation 35.19 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD | 60.6 h*ng/mL | Geometric Coefficient of Variation 23.01 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD | 147 h*ng/mL | Geometric Coefficient of Variation 19.51 |
| SAD GB002 15 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD | 214 h*ng/mL | Geometric Coefficient of Variation 28.55 |
| SAD GB002 30 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUClast), SAD | 423 h*ng/mL | Geometric Coefficient of Variation 44.51 |
Primary
PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD
Time frame: Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD | Day 1 | 355 h*ng/mL | Geometric Coefficient of Variation 25.9 |
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD | Day 7 | 462 h*ng/mL | Geometric Coefficient of Variation 13.6 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD | Day 1 | 870 h*ng/mL | Geometric Coefficient of Variation 38.1 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD | Day 7 | 827 h*ng/mL | Geometric Coefficient of Variation 20.2 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD | Day 1 | 1690 h*ng/mL | Geometric Coefficient of Variation 39.6 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC0-24), MAD | Day 7 | 1870 h*ng/mL | Geometric Coefficient of Variation 42.2 |
Primary
PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD
Time frame: Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD | Day 1 | 146 ng/ml | Geometric Coefficient of Variation 35.4 |
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD | Day 7 | 193 ng/ml | Geometric Coefficient of Variation 27 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD | Day 1 | 229 ng/ml | Geometric Coefficient of Variation 55.1 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD | Day 7 | 246 ng/ml | Geometric Coefficient of Variation 49 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD | Day 1 | 571 ng/ml | Geometric Coefficient of Variation 26 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Cmax After Dose 1, MAD | Day 7 | 528 ng/ml | Geometric Coefficient of Variation 61.8 |
Primary
PK Analysis of Inhaled GB002: Rac for AUC0-24, MAD
Time frame: Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Rac for AUC0-24, MAD | 1.30 ratio | Geometric Coefficient of Variation 25.6 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Rac for AUC0-24, MAD | 0.985 ratio | Geometric Coefficient of Variation 23.5 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Rac for AUC0-24, MAD | 1.11 ratio | Geometric Coefficient of Variation 16.8 |
Primary
PK Analysis of Inhaled GB002: Rac for Ctrough, MAD
Time frame: Days 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Rac for Ctrough, MAD | 1.66 ratio | Geometric Coefficient of Variation 27.1 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Rac for Ctrough, MAD | 0.844 ratio | Geometric Coefficient of Variation 41 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Rac for Ctrough, MAD | 1.12 ratio | Geometric Coefficient of Variation 19.2 |
Primary
PK Analysis of Inhaled GB002: t1/2, MAD
Time frame: Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: t1/2, MAD | 4.41 hours | Geometric Coefficient of Variation 7.04 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: t1/2, MAD | 4.68 hours | Geometric Coefficient of Variation 18.2 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: t1/2, MAD | 5.75 hours | Geometric Coefficient of Variation 22.4 |
Primary
PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD
Time frame: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD | 0.0833 hours |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD | 0.0500 hours |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD | 0.0500 hours |
| SAD GB002 15 mg QD | PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD | 0.0500 hours |
| SAD GB002 30 mg QD | PK Analysis of Inhaled GB002: Time to Cmax (Tmax), SAD | 0.0833 hours |
Primary
PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD
Time frame: Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD | Day 1 | 0.0833 hours |
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD | Day 7 | 0.0833 hours |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD | Day 1 | 0.0833 hours |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD | Day 7 | 0.0833 hours |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD | Day 1 | 0.0833 hours |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Tmax After Dose 1, MAD | Day 7 | 0.0833 hours |
Primary
PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD
Time frame: Days 1 and 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD | Day 1 | 1.27 h*ng/mL | Geometric Coefficient of Variation 65.4 |
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD | Day 7 | 2.11 h*ng/mL | Geometric Coefficient of Variation 51.9 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD | Day 1 | 2.60 h*ng/mL | Geometric Coefficient of Variation 55.3 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD | Day 7 | 2.54 h*ng/mL | Geometric Coefficient of Variation 26 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD | Day 1 | 3.83 h*ng/mL | Geometric Coefficient of Variation 30.4 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Trough Plasma Concentration (Ctrough), MAD | Day 7 | 4.29 h*ng/mL | Geometric Coefficient of Variation 24.7 |
Primary
PK Analysis of Inhaled GB002: Vz/F, MAD
Time frame: Day 7: 0 hour (predose), and then at 3, 10, 20, 30, 40 minutes, and 1, 2, 4, 8, 12, 24, 36, and 48 hours after the start of study treatment administration
Population: PK population: all participants who received active study drug and had at least one quantifiable postdose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | PK Analysis of Inhaled GB002: Vz/F, MAD | 495 L | Geometric Coefficient of Variation 9.46 |
| SAD GB002 3.75 mg QD | PK Analysis of Inhaled GB002: Vz/F, MAD | 588 L | Geometric Coefficient of Variation 18.55 |
| SAD GB002 7.5 mg QD | PK Analysis of Inhaled GB002: Vz/F, MAD | 604 L | Geometric Coefficient of Variation 29.81 |
Other Pre-specified
Change From Baseline in Hemoglobin
Measurement of hemoglobin
Time frame: SAD: from baseline to 11 days, MAD: from baseline to 35 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | Change From Baseline in Hemoglobin | 0.08 g/dL | Standard Deviation 0.573 |
| SAD GB002 3.75 mg QD | Change From Baseline in Hemoglobin | -0.62 g/dL | Standard Deviation 0.631 |
| SAD GB002 7.5 mg QD | Change From Baseline in Hemoglobin | -0.50 g/dL | Standard Deviation 0.447 |
| SAD GB002 15 mg QD | Change From Baseline in Hemoglobin | -0.30 g/dL | Standard Deviation 0.721 |
| SAD GB002 30 mg QD | Change From Baseline in Hemoglobin | 0.00 g/dL | Standard Deviation 0.41 |
| SAD GB002 48 mg QD | Change From Baseline in Hemoglobin | -0.53 g/dL | Standard Deviation 0.599 |
| MAD GB002 Placebo BID/TID | Change From Baseline in Hemoglobin | -0.27 g/dL | Standard Deviation 0.683 |
| MAD GB002 18 mg BID | Change From Baseline in Hemoglobin | -1.13 g/dL | Standard Deviation 0.723 |
| MAD GB002 24 mg TID | Change From Baseline in Hemoglobin | -1.13 g/dL | Standard Deviation 0.314 |
| MAD GB002 48 mg TID | Change From Baseline in Hemoglobin | -0.48 g/dL | Standard Deviation 0.512 |
Other Pre-specified
Change From Baseline in Kidney Function Parameters
Measurement of blood urea nitrogen (BUN) and creatinine.
Time frame: SAD: from baseline to 11 days, MAD: from baseline to 35 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD GB002 Placebo QD | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | -1.50 mg/dL | Standard Deviation 3.689 |
| SAD GB002 Placebo QD | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | -0.01 mg/dL | Standard Deviation 0.099 |
| SAD GB002 3.75 mg QD | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | -0.17 mg/dL | Standard Deviation 2.787 |
| SAD GB002 3.75 mg QD | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | 0.03 mg/dL | Standard Deviation 0.052 |
| SAD GB002 7.5 mg QD | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | 0.83 mg/dL | Standard Deviation 2.994 |
| SAD GB002 7.5 mg QD | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | 0.02 mg/dL | Standard Deviation 0.075 |
| SAD GB002 15 mg QD | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | -0.17 mg/dL | Standard Deviation 2.994 |
| SAD GB002 15 mg QD | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | 0.00 mg/dL | Standard Deviation 0.089 |
| SAD GB002 30 mg QD | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | 0.03 mg/dL | Standard Deviation 0.151 |
| SAD GB002 30 mg QD | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | -0.33 mg/dL | Standard Deviation 5.317 |
| SAD GB002 48 mg QD | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | -0.01 mg/dL | Standard Deviation 0.069 |
| SAD GB002 48 mg QD | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | 2.29 mg/dL | Standard Deviation 2.289 |
| MAD GB002 Placebo BID/TID | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | -0.03 mg/dL | Standard Deviation 0.052 |
| MAD GB002 Placebo BID/TID | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | 0.00 mg/dL | Standard Deviation 4.05 |
| MAD GB002 18 mg BID | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | 0.83 mg/dL | Standard Deviation 1.722 |
| MAD GB002 18 mg BID | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | -0.07 mg/dL | Standard Deviation 0.082 |
| MAD GB002 24 mg TID | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | -1.67 mg/dL | Standard Deviation 1.966 |
| MAD GB002 24 mg TID | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | 0.10 mg/dL | Standard Deviation 0.253 |
| MAD GB002 48 mg TID | Change From Baseline in Kidney Function Parameters | Change of Urea Nitrogen (BUN) Concentration | -0.33 mg/dL | Standard Deviation 3.724 |
| MAD GB002 48 mg TID | Change From Baseline in Kidney Function Parameters | Change of Creatinine Concentration | -0.02 mg/dL | Standard Deviation 0.041 |
Other Pre-specified
Change From Baseline in Liver Function Parameters
Measurement of liver function (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]).
Time frame: SAD: from baseline to 11 days, MAD: from baseline to 35 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD GB002 Placebo QD | Change From Baseline in Liver Function Parameters | AST | 0.40 U/L | Standard Deviation 3.098 |
| SAD GB002 Placebo QD | Change From Baseline in Liver Function Parameters | ALT | -0.10 U/L | Standard Deviation 7.203 |
| SAD GB002 3.75 mg QD | Change From Baseline in Liver Function Parameters | AST | -1.17 U/L | Standard Deviation 5.269 |
| SAD GB002 3.75 mg QD | Change From Baseline in Liver Function Parameters | ALT | -0.50 U/L | Standard Deviation 6.025 |
| SAD GB002 7.5 mg QD | Change From Baseline in Liver Function Parameters | AST | 2.50 U/L | Standard Deviation 2.811 |
| SAD GB002 7.5 mg QD | Change From Baseline in Liver Function Parameters | ALT | 1.17 U/L | Standard Deviation 1.472 |
| SAD GB002 15 mg QD | Change From Baseline in Liver Function Parameters | AST | 1.17 U/L | Standard Deviation 4.75 |
| SAD GB002 15 mg QD | Change From Baseline in Liver Function Parameters | ALT | -0.17 U/L | Standard Deviation 2.563 |
| SAD GB002 30 mg QD | Change From Baseline in Liver Function Parameters | ALT | 0.67 U/L | Standard Deviation 3.204 |
| SAD GB002 30 mg QD | Change From Baseline in Liver Function Parameters | AST | 0.17 U/L | Standard Deviation 2.401 |
| SAD GB002 48 mg QD | Change From Baseline in Liver Function Parameters | ALT | -1.14 U/L | Standard Deviation 4.634 |
| SAD GB002 48 mg QD | Change From Baseline in Liver Function Parameters | AST | -1.29 U/L | Standard Deviation 2.563 |
| MAD GB002 Placebo BID/TID | Change From Baseline in Liver Function Parameters | ALT | -2.83 U/L | Standard Deviation 7.653 |
| MAD GB002 Placebo BID/TID | Change From Baseline in Liver Function Parameters | AST | -1.17 U/L | Standard Deviation 3.125 |
| MAD GB002 18 mg BID | Change From Baseline in Liver Function Parameters | AST | -0.67 U/L | Standard Deviation 3.077 |
| MAD GB002 18 mg BID | Change From Baseline in Liver Function Parameters | ALT | -0.50 U/L | Standard Deviation 3.886 |
| MAD GB002 24 mg TID | Change From Baseline in Liver Function Parameters | AST | 1.17 U/L | Standard Deviation 7.782 |
| MAD GB002 24 mg TID | Change From Baseline in Liver Function Parameters | ALT | 3.50 U/L | Standard Deviation 13.096 |
| MAD GB002 48 mg TID | Change From Baseline in Liver Function Parameters | AST | -4.17 U/L | Standard Deviation 3.43 |
| MAD GB002 48 mg TID | Change From Baseline in Liver Function Parameters | ALT | -2.17 U/L | Standard Deviation 4.997 |
Other Pre-specified
Change From Baseline in White Blood Cell Count
Measurement of white blood cell count
Time frame: SAD: from baseline to 11 days, MAD: from baseline to 35 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD GB002 Placebo QD | Change From Baseline in White Blood Cell Count | 0.42 10^9 cells/L | Standard Deviation 1.212 |
| SAD GB002 3.75 mg QD | Change From Baseline in White Blood Cell Count | -0.07 10^9 cells/L | Standard Deviation 1.417 |
| SAD GB002 7.5 mg QD | Change From Baseline in White Blood Cell Count | -0.25 10^9 cells/L | Standard Deviation 1.334 |
| SAD GB002 15 mg QD | Change From Baseline in White Blood Cell Count | -0.93 10^9 cells/L | Standard Deviation 1.694 |
| SAD GB002 30 mg QD | Change From Baseline in White Blood Cell Count | -0.75 10^9 cells/L | Standard Deviation 1.294 |
| SAD GB002 48 mg QD | Change From Baseline in White Blood Cell Count | -0.16 10^9 cells/L | Standard Deviation 0.875 |
| MAD GB002 Placebo BID/TID | Change From Baseline in White Blood Cell Count | -0.28 10^9 cells/L | Standard Deviation 0.768 |
| MAD GB002 18 mg BID | Change From Baseline in White Blood Cell Count | 0.27 10^9 cells/L | Standard Deviation 0.922 |
| MAD GB002 24 mg TID | Change From Baseline in White Blood Cell Count | 0.65 10^9 cells/L | Standard Deviation 1.176 |
| MAD GB002 48 mg TID | Change From Baseline in White Blood Cell Count | -0.05 10^9 cells/L | Standard Deviation 0.689 |