Safety, Tolerability and Pharmacokinetics (PK) of RV1162 in Healthy Subjects and COPD Patients

NCT01970618 | Completed Phase 1

• 2 other identifiers: EST0012013 002329-44
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

RV1162 is a new medicine being developed for possible treatment of smoking related lung disease (also known as chronic obstructive pulmonary disease - COPD). The main purpose of this study is to investigate the safety, tolerability and pharmacokinetics of single and repeat doses of RV1162.

Conditions

Chronic Obstructive Pulmonary Disease (COPD); Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• Incidence of treatment emergent adverse events

  Assessment of the number of adverse events reported by subject following dosing

  Cohorts 1 & 2, 42 days: Cohort 3, 15 days: Cohort 4, 21 days: Cohorts 5 & 6, 28 days,

• ECG assessment (12-lead ECG)

  Change from pre-dose values

  Cohorts 1 & 2, 42 days: Cohort 3, 15 days: Cohort 4, 21 days: Cohorts 5 & 6, 28 days

• Vital sign assessment (blood pressure and heart rate)

  Change from pre-dose values

  Cohorts 1 & 2, 42 days: Cohort 3, 15 days: Cohort 4, 21 days: Cohorts 5 & 6, 28 days

• Spirometry assessment (FEV1 & FVC)

  Change from pre-dose values

  Cohorts 1 & 2, 42 days: Cohort 3, 15 days: Cohort 4, 21 days: Cohorts 5 & 6, 28 days

• Clinical laboratory assessments (blood and urine samples)

  Change from pre-dose values

  Cohorts 1 & 2, 42 days: Cohort 3, 15 days: Cohort 4, 21 days: Cohorts 5 & 6, 28 days

Secondary Outcomes (1)

• Plasma RV1162 levels

  Part A: Cohorts 1 & 2 x 4 treatment periods (TP), Cohort 3 x 1 TP (0, 10, 15 & 30 min, 1 ,2, 4, 6, 8, 10, 12 & 24h post-dose) each TP; Part B (Cohort 4): 34 samples up to 21 days post-dose; Part C (Cohorts 5 & 6): 46 samples up to 28 days post-dose

Other Outcomes (4)

• Serum biomarkers

  Part C only: Day 1&14 (0,4&24h), Day 7 (0h), Day 28

• Exhaled breath condensate

  Part C only: Screening, Days 1&14 (0&6h)

• Pulmonary plethysmography

  Part C only: Admission, Day 14 (0h)

Study Arms (3)

Part A: single dose escalation (healthy subjects)

EXPERIMENTAL

Drug: RV1162 single dose; Drug: RV1162 matching placebo single dose

Part B: 7 day repeat dose (healthy subjects)

EXPERIMENTAL

Drug: RV1162: 7 day repeat dose; Drug: RV1162 matching placebo: 7 day repeat dose

Part C: 14 day repeat dose (COPD patients)

EXPERIMENTAL

Drug: RV1162: 14 day repeat dose; Drug: RV1162 matching placebo: 14 day repeat dose

Interventions

RV1162 single dose DRUG

Safety and tolerability of single escalating doses

Part A: single dose escalation (healthy subjects)

RV1162 matching placebo single dose DRUG

Safety and tolerability of single escalating doses

Part A: single dose escalation (healthy subjects)

RV1162: 7 day repeat dose DRUG

Safety and tolerability of a repeat dose

Part B: 7 day repeat dose (healthy subjects)

RV1162 matching placebo: 7 day repeat dose DRUG

Safety and tolerability of a repeat dose

Part B: 7 day repeat dose (healthy subjects)

RV1162: 14 day repeat dose DRUG

Safety and tolerability of repeat escalating doses

Part C: 14 day repeat dose (COPD patients)

RV1162 matching placebo: 14 day repeat dose DRUG

Safety and tolerability of repeat escalating doses

Part C: 14 day repeat dose (COPD patients)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
• If a woman of childbearing potential, must have a documented menstrual period prior to the first dose and be willing and able to use 2 forms of contraception from screening until 4 months after the final dose of RV1162. Must not be a woman of child bearing potential for subjects in Part C, OR
• If a woman of non-childbearing potential must be amenorrhoeic for at least 1 year with an appropriate clinical profile, OR
• If a man, must be willing and able to use one of the contraception methods listed in the protocol and agree not to donate sperm, from the first dose until 4 months after the final dose of RV1162.
• Have a 12-lead ECG consistent with normal cardiac function
• Capable of complying with all study restrictions and procedures including ability to use the study inhaler correctly.
• Parts A \& B (healthy volunteers only)
• Aged between 18 and 50 years of age inclusive, at the time of signing the informed consent
• Healthy as determined by a physician, based on a full medical evaluation including medical history, physical examination and laboratory tests.
• Vital sign assessments within normal ranges
• Body mass index between 19 and 30 kg/m2 and body weight not less than 50 kg.
• Spirometry readings (FEV1 and FVC) to be ≥80% predicted value and FEV1/FVC ratio \>0.7 at screening
• Are not taking prescription medications (with the exception of contraceptive or hormone replacement therapies) for 14 days prior to screening and agree not to use prescription medications throughout the duration of the study.
• Not taking over the counter medications for 14 days prior to screening and up to the final follow-up visit
• Part C (COPD patients only)

You may not qualify if:

• Upper or lower respiratory tract infection within 4 weeks of screening
• Clinically significant abnormal values for haematology, clinical chemistry or urinalysis at screening
• History of, or a reason to believe a subject has a history of drug or alcohol abuse within the past 5 years
• Positive test for alcohol or drugs of abuse at screening or prior to dosing
• History of clinically significant allergies that would contraindicate participation
• Known allergy to the study drug or any of the excipients of the formulation
• Donated blood or blood products or had substantial loss of blood (more than 500 mL) within 3 months study drug or intention to donate blood or blood products during the study.
• Received an experimental drug or used an experimental medical device within 3 months or within a period less than 5 times the drug's half-life, whichever is longer, before the first dose of the study drug is scheduled.
• If a woman, has a positive pregnancy test at screening or admission, is pregnant, breast-feeding or planning to become pregnant during the study, or is a woman of child bearing potential (subjects in Part C).
• Positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B virus (HBV) infection, or hepatitis C antibodies.
• Preplanned surgery or procedures that would interfere with the conduct of the study.
• Employee of the Investigator or study centre, with direct involvement in the proposed study or other studies under the direction of that Investigator or study centre, as well as family members of the employees or the Investigator.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities
• History of regular alcohol consumption within 6 months of the study of an average weekly intake of \>21 units for males, or \>14 units for females
• The subject is unable or unwilling to comply fully with the study protocol

Sponsors & Collaborators

• Respivert Ltd: lead

Study Sites (1)

Unknown Facility

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jerome Boscia, MD

  Sponsor GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 28, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 20, 2014

Record last verified: 2014-11

Locations

GB (1)