Clinical trial NCT03235726: Study of Safety and Drug Levels of CCI15106 Inhalation Powder in Healthy Adults and Adults With Moderate Chronic Obstructive Pulmonary Disease. Study of CCI15106 Levels in People Standing Near the Person Inhaling the Drug
Official title: A Double-blind (Sponsor Unblind), Randomized, Placebo-controlled, Single and Repeat Escalating Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of CCI15106 Inhalation Powder in Healthy Participants and Participants With Moderate Chronic Obstructive Pulmonary Disease (COPD) Including Evaluation of Environmental and Healthy By-stander Exposure Levels During Dosing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: bystander
inhalation powder
monodose device
COPD
pharmacokinetics
safety
Healthy
CCI15106
tolerability
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-08-01
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In this study, subjects will be randomized to receive either study drug or placebo in a parallel manner.
Primary purpose: TREATMENT

Brief summary: This single and repeat increasing dose study will collect information on safety, tolerability and drug levels in the body of the CCI15106 inhalation powder. The study will also look at the level of CCI15106 that will be released into the air and may be found in the blood of the people standing around the person inhaling it (bystanders). This is a two-part study in which Part 1 will enroll healthy subjects and look at environmental and bystander exposure and Part 2 will enroll subjects with moderate COPD. Approximately 36 healthy subjects and approximately 22 subjects with COPD will be randomized in this study for dosing. The total study duration will be 82 days for Cohort A Part 1; 75 days for Cohort B Part 1 and Cohort C Part 1; 77 days for Cohort A Part 2; and 90 days for Cohort B Part 2.


Eligibility criteria: Some important Inclusion Criteria:

For healthy subjects and bystanders:

* 18 to 65 years of age.
* Healthy as determined by a doctor.
* Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period.
* Women who are not pregnant or breastfeeding, and not of childbearing potential.

For subjects with COPD:

* 40 to 75 years of age.
* Diagnosed with moderate COPD by a doctor.
* Have breathing test results that are consistent with moderate COPD as defined in the study protocol.
* A smoker or an ex-smoker.
* Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period.
* Women who are not pregnant or breastfeeding, and not of childbearing potential.

Some Important Exclusion Criteria:

For healthy subjects and bystanders:

* History of liver disease.
* Use of over-the-counter or prescription drugs (including vitamins) 7 days before the study until completion of the follow-up visit.
* Participation in the study would result in loss of more than 500 milliliter (mL) of blood within 3 months.
* Participation in another clinical trial with an investigational product within about 3 months before this study.
* Positive drug/alcohol screen.
* Regular use of known drugs of abuse.
* Regular alcohol consumption within 3 months before the study.
* Breath test indicative of smoking at study start.
* Documented lactose allergy/intolerance.
* Men whose partner is pregnant or breastfeeding cannot participate.
* Certain blood test results may not allow subjects to participate, as described in the study protocol.

For subjects with COPD:

* History of liver disease.
* Poorly controlled COPD disease as, for example, more than 2 exacerbations of COPD per year.
* Some respiratory conditions, like for example active tuberculosis, lung cancer or any other respiratory condition. Subjects with other respiratory conditions (for example, clinically significant: asthma, pulmonary fibrosis, bronchiectasis) are excluded if these conditions are the primary cause of their respiratory symptoms.
* Unstable or uncontrolled cardiac disease.
* Problems with kidney function as defined in the study protocol.
* Past or current medical conditions or diseases that are not well controlled.
* Subjects are not allowed to take oral corticosteroids from 4 weeks prior to screening and for the duration of the study.
* Subjects taking medications for any chronic conditions have to be on stable doses for 4 weeks before screening and until after study treatment is finished.
* Use of short-acting inhaled bronchodilators is allowed, but subjects must be able to stop their medications several times during the study.
* Use of long-acting bronchodilators is allowed, but subjects must be able to change the schedule of their medications twice during the study.
* Participation in the study would result in loss of more than 500 mL within 3 months.
* Participation in another clinical trial with an investigational product within about 3 months before this study.
* Positive drug/alcohol screen.
* Regular use of known drugs of abuse.
* Regular alcohol consumption within 3 months before the study.
* Unable to refrain from smoking for certain periods during the study (maximum about 6 hours).
* Documented lactose allergy/intolerance.
* Men whose partner is pregnant or breastfeeding cannot participate.
* Certain blood test results may not allow subjects to participate, as described in the study protocol.

Primary outcomes:
measure: Part 1 Cohort A: Number of Participants With Non-serious Adverse Events (NSAEs) and Serious Adverse Events (SAEs) in CCI15106
timeFrame: Up to 51 days
measure: Part 1 Cohort B: Number of Participants With NSAEs and SAEs in CCI15106
timeFrame: Up to 46 days
measure: Part 1 Cohort C: Number of Participants With NSAEs and SAEs in Bystanders
timeFrame: Up to 46 days
measure: Part 2 Cohort A: Number of Participants With NSAEs and SAEs
timeFrame: Up to 33 days
measure: Part 2 Cohort B: Number of Participants With NSAEs and SAEs
timeFrame: Up to 46 days
measure: Part 1: Number of Participants With Hematology Values of Potential Clinical Importance (PCI) in CCI15106
timeFrame: Up to 51 days
measure: Part 1: Number of Participants With Hematology Values of PCI in Bystanders
timeFrame: Up to 46 days
measure: Part 2: Number of Participants With Hematology Values of PCI
timeFrame: Up to 46 days
measure: Part 1: Number of Participants With Clinical Chemistry Values of PCI in CCI15106
timeFrame: Up to 51 days
measure: Part 1: Number of Participants With Clinical Chemistry Values of PCI in Bystanders
timeFrame: Up to 46 days
measure: Part 2: Number of Participants With Clinical Chemistry Values of PCI
timeFrame: Up to 46 days
measure: Part 1 Cohort A: Potential of Hydrogen (pH) Value by Visit- CCI15106 60 mg SD
timeFrame: Baseline (Day -1) and Day 2
measure: Part 1 Cohort A: pH Value by Visit- CCI15106 120 mg SD
timeFrame: Day 5
measure: Part 1 Cohort A: pH Value by Visit- CCI15106 30 mg BID
timeFrame: Days 12 and 22
measure: Part 1 Cohort B: pH Value by Visit- CCI15106 60 mg BID
timeFrame: Baseline (Day -1), Days 7 and 15
measure: Part 1: pH Value by Visit- Placebo
timeFrame: Baseline (Day -1), Days 2, 5, 7, 12, 15 and 22
measure: Part 1 Cohort C: pH Value by Visit- CCI15106 in Bystanders
timeFrame: Baseline (Day -1), Days 7 and 15
measure: Part 2 Cohort A: pH Value by Visit- CCI15106
timeFrame: Baseline (Day -1) and Day 2
measure: Part 2 Cohort B: pH Value by Visit- CCI15106 60 mg BID
timeFrame: Baseline (Day -1), Days 7 and 15
measure: Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 60 mg SD
timeFrame: Baseline (Day -1) and Day 2
measure: Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 120 mg SD
timeFrame: Day 5
measure: Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 30 mg BID
timeFrame: Days 12 and 22
measure: Part 1 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID
timeFrame: Baseline (Day -1), Days 7 and 15
measure: Part 1: Specific Gravity Value by Visit- Placebo
timeFrame: Baseline (Day -1), Days 2, 5, 7, 12, 15 and 22
measure: Part 1 Cohort C: Specific Gravity Value by Visit- CCI15106 in Bystanders
timeFrame: Baseline (Day -1), Days 7 and 15
measure: Part 2 Cohort A: Specific Gravity Value by Visit- CCI15106
timeFrame: Baseline (Day -1) and Day 2
measure: Part 2 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID
timeFrame: Baseline (Day -1), Days 7 and 15
measure: Part 1: Number of Participants With Worst Case Post-Baseline 12-lead Electrocardiogram (ECG) of PCI in CCI15106
timeFrame: Up to 51 days
measure: Part 1: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI in Bystander
timeFrame: Up to 46 days
measure: Part 2: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI
timeFrame: Up to 46 days
measure: Part 1: Number of Participants With Abnormal Telemetry Findings
timeFrame: Days 1, 3, 6, 7, 12 and 18: 0.5 hour (pre-dose) to 4 hours post-dose
measure: Part 2: Number of Participants With Abnormal Telemetry Findings
timeFrame: Days 1, 7, 12 and 13: 0.5 hour (pre-dose) to 4 hours post-dose
measure: Part 1: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Indicated Time Points
timeFrame: Days 1, 3, 6 and 19: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 8, 11 and 16: pre-dose and 4 hours post-dose; Day 14: pre-dose, 0.5, 1 and 4 hours post-dose
measure: Part 1: Percent Predicted Forced Vital Capacity (FVC) at Indicated Time Points
timeFrame: Days 1, 3, 6 and 19: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 8, 11 and 16: pre-dose and 4 hours post-dose; Day 14: pre-dose, 0.5, 1 and 4 hours post-dose
measure: Part 2: Percent Predicted FEV1 at Indicated Time Points
timeFrame: Day 1 and 14: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 3, 6 and 11: pre-dose and 4 hours post-dose
measure: Part 2: Percent Predicted FVC at Indicated Time Points
timeFrame: Day 1 and 14: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 3, 6 and 11: pre-dose and 4 hours post-dose
measure: Part 1: Number of Participants With Vital Signs Values of PCI
timeFrame: Up to 51 days
measure: Part 1: Number of Participants With Vital Signs Values of PCI in Bystanders
timeFrame: Up to 46 days
measure: Part 2: Number of Participants With Vital Signs Values of PCI
timeFrame: Up to 46 days
measure: Part 1 Cohort A: Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose
measure: Part 1 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 120 mg on Day 3
timeFrame: Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 2 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: Maximum Observed Plasma Concentration (Cmax) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose
measure: Part 1 Cohort A: Cmax After Single Dose Administration of CCI15106 120 mg on Day 3
timeFrame: Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 2 Cohort A: Cmax After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: Time of Maximum Concentration (Tmax) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose
measure: Part 1 Cohort A: Tmax After Single Dose Administration of CCI15106 120 mg on Day 3
timeFrame: Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 2 Cohort A: Tmax After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: AUC From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose
measure: Part 1 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 120 mg on Day 3
timeFrame: Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 2 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: Elimination Half-life (t1/2) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose
measure: Part 1 Cohort A: t1/2 After Single Dose Administration of CCI15106 120 mg on Day 3
timeFrame: Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 2 Cohort A: t1/2 After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: Clearance (CL/F) After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose
measure: Part 1 Cohort A: CL/F After Single Dose Administration of CCI15106 120 mg on Day 3
timeFrame: Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 2 Cohort A: CL/F After Single Dose Administration of CCI15106 60 mg on Day 1
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: AUC From Time Zero to End of Dosing Interval (AUC[0-tau]) After Repeated Dose Administration of CCI15106 30 mg
timeFrame: Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 1 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Days 1 and 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose
measure: Part 2 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Days 1 and 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose
measure: Part 1 Cohort A: Cmax After Repeated Dose Administration of CCI15106 30 mg
timeFrame: Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 1 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 2 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: Tmax After Repeated Dose Administration of CCI15106 30 mg
timeFrame: Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 1 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 2 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1 Cohort A: t1/2 After Repeated Dose Administration of CCI15106 30 mg
timeFrame: Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose
measure: Part 1 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 2 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg
timeFrame: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Part 1: Concentration of CCI15106 in Plasma of Bystanders: Cohort C
timeFrame: Days 1, 7 and 14: pre-dose, 15 minutes post-dose
measure: Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Bystander: Cohort C
timeFrame: Days 1, 7 and 14: 15 minutes post-dose
measure: Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Stationary Pumps: Cohort C
timeFrame: Days 1, 7 and 14: 20 and 60 minutes post-dose
Secondary outcomes:
measure: Part 1: Concentration of CCI15106 in Lung Epithelial Lining Fluid (ELF) in Repeated Dose of Cohort B 60 mg
timeFrame: Up to Day 13
measure: Part 2: Concentration of CCI15106 in ELF in Repeated Dose of Cohort B 60 mg
timeFrame: Up to Day 13
measure: Part 1: Number of Participants With Medical Device Incidents in CCI15106
timeFrame: Up to Day 19
Other outcomes:
Locations:
city: Park Royal
country: United Kingdom
facility: GSK Investigational Site
state: London
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Dumont EF, Oliver AJ, Ioannou C, Billiard J, Dennison J, van den Berg F, Yang S, Chandrasekaran V, Young GC, Lahiry A, Starbuck DC, Harrell AW, Georgiou A, Hopchet N, Gillies A, Baker SJ. A Novel Inhaled Dry-Powder Formulation of Ribavirin Allows for Efficient Lung Delivery in Healthy Participants and Those with Chronic Obstructive Pulmonary Disease in a Phase 1 Study. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02267-19. doi: 10.1128/AAC.02267-19. Print 2020 Apr 21.