The Effects of RPL554 in Addition to Tiotropium in COPD Patients

NCT03028142 | Completed Phase 2 Results

• 1 other identifier: RPL554-CO-202
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II, randomised, double blind, placebo controlled, complete block, three way crossover study to investigate treatment with nebulised RPL554 and tiotropium together in patients with moderate to severe chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the bronchodilator effect (opening of the airways) of RPL554 when used in combination with a long acting anti-muscarinic receptor antagonist (tiotropium) whilst dosing the RPL554 to steady state blood levels. It is planned to randomise up to 30 patients to have 24 evaluable patients at one study centre. In each treatment period, patients will receive an open label dose of tiotropium from a dry power inhaler (DPI) followed immediately by a double blind dose of either RPL554 6mg, 1.5mg or placebo (depending on treatment sequence) from a nebuliser in the morning on Day 1, Day 2 and Day 3. The dose of RPL554 or placebo will be repeated in the evening on Day 1 and Day 2; there will not be an evening dose on Day 3.

Conditions

Chronic Obstructive Pulmonary Disease Moderate

Outcome Measures

Primary Outcomes (2)

• Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing

  Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing

  Day 3

• Average FEV1 Over 12 Hours on the Third Day of Dosing

  Average FEV1 area under the curve (AUC) over 12 hours on the third day of dosing

  Day 3

Secondary Outcomes (2)

• Peak FEV1 on Day 1

  Day 1

• Average FEV1 Over 12 Hours on Day 1

  Day 1

Study Arms (3)

Lower Dose Nebulised Treatment

EXPERIMENTAL

1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days

Drug: 1.5 mg RPL554 plus tiotropium

Higher Dose Nebulised Treatment

EXPERIMENTAL

6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days

Drug: 6 mg RPL554 plus tiotropium

Placebo

PLACEBO COMPARATOR

Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days

Drug: Placebo plus tiotropium

Interventions

1.5 mg RPL554 plus tiotropium DRUG

Lower Dose Nebulised Treatment

6 mg RPL554 plus tiotropium DRUG

Higher Dose Nebulised Treatment

Placebo plus tiotropium DRUG

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• 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.
• Male or female aged between 40 and 75 years inclusive, at the time of informed consent.
• If male: must agree to meet the following from the first dose up to 1 month after the last dose of study treatment:
• Not donate sperm
• Either: be sexually abstinent in accordance with a patient's usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change) Or: use a condom with all sexual partners. If the partner is of childbearing potential the condom must be used with spermicide and a second highly effective form of contraception must also be used
• If female: either be:
• Of non-childbearing potential defined as being:
• Either: post-menopausal (being spontaneously amenorrhoeic for at least 1 year with an appropriate clinical profile \[e.g. age appropriate, history of vasomotor symptoms\]
• Or: permanently sterilised e.g. tubal occlusion, hysterectomy, bilateral oophorectomy, bilateral salpingectomy
• Of childbearing potential and agreeing to use a highly effective method of contraception until completion of the end of study visit.
• Have a 12-lead ECG recording at screening and randomisation (pre-dose in Treatment Period 1) showing the following:
• Heart rate between 45 and 90 beats per minute (bpm)
• QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤450 msec for males and ≤470 ms for females
• QRS interval ≤120 msec
• No clinically significant abnormalities (as judged by the Investigator) including morphology (e.g. left bundle branch block, atrio-ventricular nodal dysfunction, ST segment abnormalities)

You may not qualify if:

• A history of life-threatening COPD exacerbation including Intensive Care Unit admission and/or requiring intubation.
• COPD exacerbation requiring oral steroids, or lower respiratory tract infection requiring antibiotics, in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
• A history of one or more hospitalisations for COPD in the 12 months prior to screening or randomisation (pre-dose in Treatment Period 1).
• Lactation (female patients only).
• Positive urine or serum pregnancy test at screening, or a positive urine pregnancy test prior to randomisation (female patients of childbearing potential only).
• Prior exposure to RPL554 or known hypersensitivity to RPL554 or its components.
• Intolerance or hypersensitivity to tiotropium.
• Evidence of cor pulmonale.
• Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
• Previous lung resection or lung reduction surgery.
• Use of oral COPD medications (e.g. oral steroids, theophylline and romifulast) in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
• History of, or reason to believe, a patient has drug or alcohol abuse within the past 3 years.
• Inability to perform technically acceptable spirometry or whole body plethysmography (at screening or randomisation \[pre dose in Treatment Period 1\])
• Received an experimental drug within 30 days or five half lives, whichever is longer.
• Patients with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant.

Sponsors & Collaborators

• Verona Pharma plc: lead

Related Publications (1)

• Singh D, Abbott-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018 Nov 1;52(5):1801074. doi: 10.1183/13993003.01074-2018. Print 2018 Nov.

  PMID: 30166326 DERIVED

MeSH Terms

Interventions

ensifentrine; Tiotropium Bromide

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Brian Maurer
• Organization: Verona Pharma plc

brian.maurer@veronapharma.com

+19147675037

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 23, 2017
• Study Start: January 1, 2017
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: February 27, 2019
• Results First Posted: January 23, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share