A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of RV1729

NCT01813084 | Completed Phase 1

• 2 other identifiers: STN0012012-005452-42
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

Brief Summary

RV1729 is a new medicine being developed for possible treatment of asthma and 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 RV1729.

Conditions

Asthma; Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• Incidence of treatment emergent adverse events

  Assessment of the number of adverse events reported by subjects following dosing.

  Cohort 1, 49 days: Cohorts 2 & 3, 21 days; Cohorts 4, 5, 6 & 7, 28 days

• ECG Assessment (12-lead ECG)

  Change from pre-dose values.

  Cohort 1, 49 days: Cohorts 2 & 3, 21 days; Cohorts 4, 5, 6 & 7, 28 days

• Vital sign assessment (blood pressure & heart rate)

  Change from pre-dose values.

  Cohort 1, 49 days: Cohorts 2 & 3, 21 days; Cohorts 4, 5, 6 & 7, 28 days

• Spirometry assessment (FEV1 & FVC)

  Change from pre-dose values

  Cohort 1, 49 days: Cohorts 2 & 3, 21 days; Cohorts 4, 5, 6 & 7, 28 days

• Clinical laboratory assessments (blood and urine samples)

  Change from pre-dose values

  Cohort 1, 49 days: Cohorts 2 & 3, 21 days; Cohorts 4, 5, 6 & 7, 28 days

Secondary Outcomes (1)

• Plasma RV1729 levels

  Cohort 1: Day 1 (0,10,15&30min,1,2,4,6&24h), 5 treatment periods. Cohorts 2&3: Day 1 (0,10,15&30min 1,2,4,6,8,12h), Days 2-8 (24,48,72,96,120,144&168h). Cohorts 4,5,6&7: Days 1, 7&14 (0,10,15&30min,1,2,4,6,8,10,12&24h) & Days 8-13 & 16-21 & 28 (0h)

Other Outcomes (5)

• Serum biomarkers (measuring markers of inflammation in the blood)

  Cohorts 4, 5, 6 & 7: Days 1 & 14 (0, 4 & 24 h), Day 4 (0 h) and Day 28

• Exhaled Nitric Oxide (measuring airway inflammation)

  Cohorts 4, 5, 6 & 7: Screening then Days 1 & 4 (0 h), Day 14 (0, 1 & 24 h)

• Exhaled breath condensate (measuring markers of oxidative stress)

  Cohorts 4, 5, 6 & 7: Screening then Days 1 & 14 (0 & 6 h)

Study Arms (3)

Part A: single dose escalation

EXPERIMENTAL

Drug: RV1729 single dose; Drug: RV1729 matching placebo single dose

Part B: 14 day repeat dose escalation (healthy volunteers)

EXPERIMENTAL

Drug: RV1729: 14 day repeat dose; Drug: RV1729 matching placebo: 14 day repeat dose

Part C: 14 day repeat dose (asthma patients)

EXPERIMENTAL

Drug: RV1729: 14 day repeat dose; Drug: RV1729 matching placebo: 14 day repeat dose

Interventions

RV1729 single dose DRUG

Safety and tolerability of single escalating doses

Part A: single dose escalation

RV1729 matching placebo single dose DRUG

Safety and tolerability of single escalating doses

Part A: single dose escalation

RV1729: 14 day repeat dose DRUG

Safety and tolerability of repeat escalating doses

Part B: 14 day repeat dose escalation (healthy volunteers); Part C: 14 day repeat dose (asthma patients)

RV1729 matching placebo: 14 day repeat dose DRUG

Safety and tolerability of repeat escalating doses

Part B: 14 day repeat dose escalation (healthy volunteers); Part C: 14 day repeat dose (asthma patients)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be a man or woman between 18 to 50 years of age, inclusive, at the time of signing the informed consent
• 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 two forms of contraception from screening to 90 days after the final dose of RV1729, OR
• If a woman of non-childbearing potential must be amenorrhoeic for greater than 1 year or have been permanently sterilised, 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, the first dose until 90 days after they receive the final dose of RV1729.
• Body mass index between 19 and 30 kg/m2 (inclusive), and body weight not less than 50 kg
• Vital sign assessments within normal ranges: blood pressure between 90 and 140 mmHg systolic, inclusive, and between 40 and 90 mmHg diastolic; heart rate 40 - 100 bpm
• Have a 12-lead ECG consistent with normal cardiac conduction and function
• Capable of complying with all study restrictions and procedures including ability to use the study Dry Powder Inhaler correctly
• Parts A \& B (healthy volunteers only)
• Healthy as determined by a physician, based on a full medical evaluation including medical history, physical examination, laboratory tests.
• Prebronchodilator spirometry readings (FEV1 and FVC) to be ≥ 80% predicted value and FEV1/FVC ratio \> 0.7 at screening
• Are not taking prescription medications 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 visit to the final follow up visit
• Part C (asthma patients only)

You may not qualify if:

• Upper or lower respiratory tract infection within 4 weeks of the screening visit
• 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 before the study
• Received an experimental drug or used an experimental medical device within 3 months or within a period less than 10 times the drug's half life before the first dose of the study drug is scheduled
• If a woman, has a positive serum pregnancy test at screening or on admission, is pregnant, breast-feeding or planning to become pregnant during the study
• Positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B virus (HBV) infection, or hepatitis C antibodies
• History of smoking or use of nicotine-containing substances within the previous 6 months, or a positive carbon monoxide test at screening
• Preplanned surgery or procedures that would interfere with the conduct of the study
• Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, 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

Sponsors & Collaborators

• Respivert Ltd: lead

Study Sites (2)

Unknown Facility

London, NW10 7EW, United Kingdom

Location

Unknown Facility

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

6-(2-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)methyl)-3-(2-chlorobenzyl)-4-oxo-3,4-dihydroquinazolin-5-yl)-N,N-bis(2-methoxyethyl)hex-5-ynamide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

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: March 14, 2013
• First Posted: March 18, 2013
• Study Start: May 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 24, 2014

Record last verified: 2014-04

Locations

GB (2)