Inclusion Criteria.

• - Have a diagnosis of interstitial lung disease according to the American Thoracic Society Guidelines.

• - Have a chronic cough for at least 3 months prior to the screening visit.

• - Patients should be on a stable dose of ILD-directed therapies for 3 months prior to enrollment and will be allowed to continue their ILD-directed therapies.

These include -but are not limited to- corticosteroids, immunosuppressing agents such as azathioprine and mycophenolate, as well as antifibrotic medications including nintedanib and pirfenidone. Additional corticosteroids and adjustment of ILD-directed therapy doses is permitted if deemed appropriate by the treating physician.

• - Have a score of ≥ 40mm on the Cough Severity VAS at Screening.

• - Women of child-bearing potential must agree to use 2 forms of acceptable birth control and make no donation of eggs from Screening through the end of the 8-week study period.

Acceptable birth control methods include established use of oral, injected, or implanted hormonal methods of contraception; intrauterine device (IUD) or intrauterine system (IUS); tubal ligation; or male sterilization. Double-barrier method (diaphragm for female subject and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control. When concordant with the preferred lifestyle of the subject, true and complete abstinence (not periodic abstinence) is acceptable.

• - Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control, 1 of which must be a barrier method, and make no donation of sperm from Screening until 3 months after the last dose of study drug at the end of 8 weeks.

• - Have provided written informed consent.

• - Are willing and able to comply with all aspects of the protocol.

Exclusion Criteria.

• - Current smoker (cigarettes, e-cigarettes or marijuana) or former smokers who have smoked within the past 12 months.

• - Former smokers with > 20 pack-year history of smoking.

• - Ongoing treatment with an ACE-inhibitor that is considered as the potential cause of a subject's cough or requiring treatment with an ACE-inhibitor during the study or within 12 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).

• - History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Screening/Baseline Visit (Day -14 to Day 0) - History of opioid use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0).

Use of opioids for other indications (for example, to treat pain) is permitted.

• - History of baclofen use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0).

Use of baclofen for other indications (for example, to treat spasticity) is permitted.

• - Presence of an untreated or undertreated cause (other than ILD) for the patient's chronic cough (as determined by the treating/referring physician per ACCP guidelines).

e.g. uncontrolled asthma, GERD or post-nasal drainage that could potentially explain the patient's chronic cough.

• - Requiring concomitant therapy with prohibited medications (listed below).

• - Treatment with any pharmaceutical or biological investigational therapy (excluding coronavirus disease of 2019 (COVID) vaccination and COVID related monoclonal antibody therapy) - Participation in another clinical trial that does not allow co-enrollment within 4 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0) - Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x the upper limit of normal (ULN) during screening.

• - Serum creatinine < 30 mL/min, hemodialysis or peritoneal dialysis.

• - Advanced liver disease as defined by the presence of cirrhosis and/or signs of portal hypertension.

• - History of previous hypersensitivity or intolerance to Duloxetine & Amitriptyline (patients who have previously been on either amitriptyline or duloxetine for chronic cough or other reasons and have tolerated the medication will be offered participation regardless of previous response to therapy).

• - Currently pregnant or breastfeeding female subject.

• - Presence of any medical condition or disability that the investigators believe could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject.

• - Planned or anticipated major surgical procedure or other activity that would interfere with the subject's ability to comply with protocol-mandated assessments (e.g., extended travel) during the subject's participation in the study.

• - Currently taking either another SSRI, SNRI or MAO inhibitor which the patient cannot safely discontinue at least 2 weeks prior to the screening period.

Therapies that are prohibited during the 8-week blinded phase of the study: The following therapies are prohibited from 2 week prior to the Screening/Baseline Visit (Day -14 to Day 0) through the end of the 8-week blinded treatment period.

• - Opioids (of any kind including tramadol & codeine) specifically prescribed for treatment of cough.

• - Dextromethorphan.

• - Guaifenesin.

• - Chlorpheniramine.

• - Benzonatate.

• - Trazodone.

• - Pregabalin or gabapentin prescribed for chronic cough.

• - 1% tetracaine lollipops prescribed for chronic cough.

• - 4% nebulized lidocaine solution prescribed for chronic cough.

• - Any SSRI (selective serotonin reuptake inhibitor) e.g. bupropion, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine.

• - Any SNRI (serotonin-norepinephrine reuptake inhibitor) e.g. venlafaxine, desvenlafaxine, milnacipran, levomilnacipran.

• - Any Tricyclic antidepressant e.g. doxepin, clomipramine, nortriptyline, imipramine, protriptyline, amoxapine, trimipramine.

• - Any MAO (Monoamine oxidase) inhibitor.

e.g. phenelzine, selegiline, isocarboxacid or tranylcypromine.

• - Patients who were previously prescribed either amitriptyline or duloxetine for chronic cough will be eligible for the study as long as they had discontinued the medication at least 12 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).

The following therapies are prohibited from 4 week prior to the Screening/Baseline Visit (Day -14 to Day 0) through the end of the 8-week blinded treatment period. • Investigational biologic or pharmaceutical therapies (excluding COVID vaccination and COVID related monoclonal antibody therapy) The following therapies are prohibited from 12 week prior to the Screening/Baseline Visit (Day -14 to Day 0) through the end of the 8-week blinded treatment period. • Treatment with an ACE-inhibitor

This is a randomized, double-blind, placebo-controlled, parallel-arm, dose escalation study of Duloxetine & Amitriptyline in subjects with interstitial lung disease-related chronic cough. Subjects will be screened during a period of up to 2 week and will undergo screening/ baseline cough monitoring. A total of 25 subjects who meet entry criteria will be randomly assigned in a 1: 1: 1: 1: 1 ratio to one of five treatment arms using stratified randomization in blocks of 5. Each arm will have two successive 4-week treatment periods (Blinded Period 1 & 2). After this, patients will be unblinded and receive routine clinical care. During the unblinded (routine clinical care) follow up phase; subjects will be initially offered the option of continuing amitriptyline or duloxetine based on their initial randomization arm. Subjects could also choose an alternative chronic cough therapy (e.g. pregabalin, gabapentin, 1% tetracaine lollipop or nebulized lidocaine or combination therapy). Subjects in treatment arm 5, who received placebo during the 8 weeks blinded period will have a discussion regarding all available cough therapies. Patients will be offered the flexibility of therapy options during the unblinded follow up as they would during routine clinical care. Participation in the unblinded follow-up period will be optional. Treatment Arm 1: Blinded Period 1 (1st 4 weeks): 30mg of Duloxetine Blinded Period 2 (2nd 4 weeks): 30mg of Duloxetine & 30mg of Placebo Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough. Treatment Arm 2: Blinded Period 1 (1st 4 weeks): 30mg of Duloxetine Blinded Period 2 (2nd 4 weeks): 60mg of Duloxetine (2 pills of 30mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough. Treatment Arm 3: Blinded Period 1 (1st 4 weeks): 25mg of Amitriptyline Blinded Period 2 (2nd 4 weeks): 25mg of Amitriptyline + 25mg of Placebo Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough. Treatment Arm 4: Blinded Period 1 (1st 4 weeks): 25mg of Amitriptyline Blinded Period 2 (2nd 4 weeks): 50mg of Amitriptyline (2 pills of 25mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough. Treatment Arm 5: Blinded Period 1 (1st 4 weeks): 30mg of Placebo Blinded Period 2 (2nd 4 weeks): 60mg of Placebo (2 pills of 30mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough

Arms

Experimental: Duloxetine and Placebo

Subjects will receive 30mg of Duloxetine for blinded period 1 (first 4 week treatment period) and 30mg of Duloxetine plus 30mg Placebo for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Experimental: Duloxetine dose escalation

Subjects will receive 30mg of Duloxetine for blinded period 1 (first 4 week treatment period) and 60mg of Duloxetine for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Experimental: Amitriptyline and Placebo

Subjects will receive 25mg of Amitriptyline for blinded period 1 (first 4 week treatment period) and 25mg of Amitriptyline plus 30mg Placebo for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Experimental: Amitriptyline dose escalation

Subjects will receive 25mg of Amitriptyline for blinded period 1 (first 4 week treatment period) and 50mg of Amitriptyline for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Placebo Comparator: Placebo

Subjects will receive 30mg of Placebo for blinded period 1 (first 4 week treatment period) and 60mg of Placebo for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Interventions

Drug: - Amitriptyline 25 MG

25 mg orally for 4 weeks

Drug: - Amitriptyline 50 MG

50 mg orally for 4 weeks

Drug: - Duloxetine 30 MG

30mg orally for 4 weeks

Drug: - Duloxetine 60 MG

60mg orally for 4 weeks

Drug: - Placebo 30 MG

30mg tablet with no active study ingredient for 4 weeks

Drug: - Placebo 60 MG

60mg tablet with no active study ingredient for 4 weeks