A Dose-ranging Study of Orvepitant in Patients With Chronic Refractory Cough

A multi-center, double-blind, randomized, parallel group, placebo-controlled dose range study
in subjects with chronic refractory cough (CRC).

Doses of orvepitant (10 mg/day, 20 mg/day and 30 mg/day) and placebo will be investigated in
four parallel groups.

Each group will compromise of approximately 61 subjects, randomized 1:1:1:1 (approximately
244 subjects in total).

All subjects will enter a three-week screening period to determine eligibility. Eligible
subjects will be randomized at the Baseline/Day 1 visit and enter a 12-week double-blind
dosing period. During this period there will be four visits at Weeks 2, 4, 8 and 12. There
will be a final safety follow-up visit at Week 14.

Key Inclusion Criteria:

- Male and female subjects ≥18 years of age.

- Diagnosis of CRC or unexplained cough for at least 1 year (see ACCP/BTS guidelines
attached).

- A awake average cough frequency of ≥10 coughs/ hour, as assessed using an ACM during
the screening period.

Key Exclusion Criteria:

- Subjects with respiratory tract infection (<4 weeks prior to study start)

- Current smokers or ex-smokers with <6 months' abstinence or cumulative history of >10
pack years

- Treatment with Angiotensin Converting Enzyme (ACE) inhibitors within 3 months of
screening

- FEV1 <80% predicted, measured at screening using spirometry

- History of cystic fibrosis, idiopathic pulmonary fibrosis, clinically significant
bronchiectasis, moderate to severe asthma, chronic obstructive pulmonary disease
(COPD)

- Any clinically significant abnormal laboratory test result(s)

- Inability to comply with the use of prohibited and allowed medications as described in
the protocol.