Dose Escalating Study of CCI15106 Inhalation Capsules in Healthy Subjects and Moderate Chronic Obstructive Pulmonary Disease (COPD) Patients

NCT ID: NCT03243760

Last Updated: 2020-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-10

Study Completion Date

2016-08-20

Brief Summary

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This study will be the first administration of CCI15106 capsules for inhalation to humans. The primary objective of the study is to investigate the safety and tolerability of single and repeat escalating doses of CCI15106 in healthy subjects and patients with moderate chronic obstructive pulmonary disease (COPD). The intention of this study is to provide sufficient confidence in the safety of the molecule delivered by inhalation to inform progression to further repeat dose and proof of concept studies.

This will be a three-part study. Part 1 will investigate single ascending doses and Part 2 repeat ascending doses in healthy subjects. In Part 3, a single dose will be administered to patients with moderate COPD.

There will be screening period of up to 30 days. The treatment period will be 3 days for Parts 1 and 3 and 16 days for Part 2. Follow-up will be performed within 30 days after the last dose.

Detailed Description

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Conditions

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Pulmonary Disease, Chronic Obstructive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Cohort A: Single dose CCI15106 7.5 mg /Placebo

Healthy subjects will receive single dose of either 1 capsule CCI15106 7.5 milligram (mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort B: Single dose CCI15106 15 mg /Placebo

Healthy subjects will receive single dose of either 15 mg CCI15106 (2 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort C: Single dose CCI15106 30 mg /Placebo

Healthy subjects will receive single dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort D: Single dose CCI15106 30 mg /Placebo-BAL

Healthy subjects will receive single dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization. BAL procedures will be performed in this cohort additionally.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort E: Single dose CCI15106 45 mg /Placebo

Healthy subjects will receive single dose of either 45 mg CCI15106 (6 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort F: Single dose CCI15106 60 mg /Placebo

Healthy subjects will receive single dose of either 60 mg CCI15106 (8 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort G: CCI15106 7.5 mg /Placebo BID 14 Days

Healthy subjects will receive repeat dose of either 7.5 mg CCI15106 (1 capsule) or matching placebo twice daily (BID) for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort H: CCI15106 15 mg /Placebo BID 14 Days

Healthy subjects will receive repeat dose of either 15 mg CCI15106 (2 capsules of 7.5 mg) or matching placebo BID for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort I: CCI15106 30 mg /Placebo BID 14 Days-BAL

Healthy subjects will receive repeat dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo BID for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization. BAL procedures will be performed in this cohort additionally.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort J: CCI15106 =<30 mg /Placebo BID 14 Days

Healthy subjects will receive repeat dose of either =\< 30 mg CCI15106 (less than or equal to 4 capsules of 7.5 mg) or matching placebo BID for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization. The dose for cohort J is unknown at this time and will depend on results seen in the previous cohorts.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort K: Single dose CCI15106 30 mg /Placebo-COPD

COPD patients will receive single dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Group Type EXPERIMENTAL

CCI15106 7.5 mg capsule

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Placebo

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Placebo-2

Intervention Type DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Interventions

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CCI15106 7.5 mg capsule

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Intervention Type DRUG

Placebo

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Intervention Type DRUG

Placebo-2

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

For Healthy Subjects

* Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
* Healthy as determined by the investigator.
* Body weight \>= 50 kilogram (kg) for males and 45 kg for females and body mass index (BMI) within the range 19 - 31 kg/meter square (m\^2) (inclusive)
* Male or Female: Male subjects with female partners of child bearing potential must comply with the contraception requirements as specified in protocol. A female subject is eligible to participate if she is of non-reproductive potential.
* Capable of giving signed informed consent.

For COPD Patients

* Between 40 and 75 years of age inclusive, at the time of signing the informed consent.
* Diagnosed with moderate COPD (GOLD class II) by a qualified physician as defined by the GOLD guidelines (http://www.goldcopd.org/).
* The subject has spirometry at screening, showing: a) post-bronchodilator forced expiratory volume in 1 second (FEV1)\>=50% and \<80% predicted normal; b) post-bronchodilator FEV1/ forced vital capacity (FVC)\<0.7.
* Subject is a smoker or an ex-smoker.
* Body weight \>= 45 kg and BMI within the range 17 - 32 kg/m\^2 (inclusive).
* Male or Female: Male subjects with female partners of child bearing potential must comply with the contraception requirements as specified in protocol. A female subject is eligible to participate if she is of non-reproductive potential.
* Capable of giving signed informed consent.

Exclusion Criteria

For Healthy Subjects

* Male partners of women who are pregnant or lactating
* Alanine transaminase (ALT) and/or bilirubin \>1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QT interval corrected for heart rate (QTc )\> 450 millisecond (msec).
* Heart rate: \<40 and \>100 beats per minute (bpm) for males and \<50 and \>100 bpm for females, PR Interval: \<120 and \>220 msec, QRS duration: \<70 and \>120 msec, QTcF interval: \>450 msec
* Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions.
* Unable to refrain from prescription or non-prescription drugs
* History of regular alcohol consumption within 3 months of the study
* Breath test indicative of smoking at day -1
* History of sensitivity to any of the study medications
* For cohorts that will undergo BAL, contraindications to bronchoalveolar lavage
* Documented lactose allergy/intolerance for cohorts with lactose placebo if they are used in the study.
* Hemoglobin (Hgb) below the lower level of the normal range with one repeat testing allowed, or known hemoglobinopathies.
* Known severe hypersensitivity reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme.
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
* A positive pre-study drug/alcohol screen.
* A positive test for human immunodeficiency virus (HIV) antibody.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 month period.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

For COPD Patients

* Male partners of women who are pregnant or lactating.
* ALT and/or bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QTc \> 450 msec or QTc \> 480 msec in subjects with Bundle Branch Block.
* Heart rate: \<40 and \>100 bpm for males and \<50 and \>100 bpm for females, PR Interval: \<120 and \>220 msec, QRS duration: \<70 and \>120 msec, QTcF interval: \>450 msec
* Subject has poorly controlled COPD as defined in protocol
* History of an upper or lower respiratory tract infection requiring antibiotics in the 4 weeks prior to screening.
* Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the subject or affect the interpretation of the results.
* Subjects who have 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.
* Patients taking medications for any chronic conditions have to be on stable doses for 4 weeks prior to screening and until after completion of the treatment period. This includes COPD maintenance therapies (e.g. inhaled corticosteroids, long-acting beta-agonists, long-acting muscarinic agonists).
* Didanosine and azathioprine are not allowed.
* Use of short-acting inhaled bronchodilators is allowed, but patients must be able to discontinue their medications twice during the study.
* Use of long-acting bronchodilators is allowed, but patients must be able to modify the schedule of their medications twice during the study.
* Unable to refrain from smoking for 2 hour (h) prior to dosing and until all assessments are complete for 4 h after dosing and also for 1 h prior to any vital signs and ECG assessments.
* History of regular alcohol consumption within 3 months of the study
* History of sensitivity to any of the study medications.
* Documented lactose allergy/intolerance
* Impaired renal function (creatinine clearance \< 50 mL/ minute).
* Known severe hypersensitivity reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme.
* Hgb below the lower level of the normal range with one repeat testing allowed or known hemoglobinopathies.
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
* A positive pre-study drug/alcohol screen.
* A positive test for HIV antibody.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 32071044 (View on PubMed)

Other Identifiers

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2015-003960-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

202031

Identifier Type: -

Identifier Source: org_study_id

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