A Study of Nalbuphine (Extended Release) ER in Idiopathic Pulmonary Fibrosis (IPF) for Treatment of Cough

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• Pulmonary Fibrosis 680
• Idiopathic Pulmonary Fibrosis 551
• Fibrosis 3,255

Keywords

• Nalbuphine
• Cough
• Idiopathic Pulmonary Fibrosis
• Pharmacokinetics

Pulmonary Fibrosis

680 studies on the registry are indexed under Pulmonary Fibrosis; 119 are open to participants now.

This study's enrollment of 42 is below the median of 50 across 419 interventional studies indexed under Pulmonary Fibrosis.

Lead sponsor

Trevi Therapeutics is the lead sponsor of 16 studies on the registry; 2 are open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 6 (67%) have results posted.

Study arms

• Experimental
  NAL ER then placebo

  Participants received NAL ER in treatment period 1 at dose 27 mg once daily (QD) to 54 mg twice daily (BID) over a 5-day period and then maintained at 54 mg BID for 4 days. Dose was increased to 108 mg BID for 1 week then to 162 mg BID for 6 days, followed by placebo matching NAL ER for 3 weeks in treatment period 2. Both the treatment periods were separated by 2 weeks of washout period.

  Drug: NAL ER · Drug: Placebo

• Experimental
  Placebo then NAL ER

  Participants received placebo matching NAL ER for 3 weeks in treatment period 1 followed by NAL ER in treatment period 2 at dose 27 mg QD to 54 mg BID over a 5-day period and then maintained at 54 mg BID for 4 days. Dose was increased to 108 mg BID for 1 week then to 162 mg BID for 6 days. Both the treatment periods were separated by 2 weeks of washout period.

  Drug: NAL ER · Drug: Placebo

Interventions

• DrugNAL ER

  Participants received NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID.

  Also known as: Nalbuphine

• DrugPlacebo

  Participants received Placebo tablet (matching NAL ER ).

  Also known as: Placebo matched to NAL ER

Primary outcomes

1. Number of Participants Who Experienced at Least One Treatment Emergent Adverse Events (TEAEs)

   An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE was defined as any AE that occurs after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.

   Time frame: Up to Day 72

2. Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

   The clinical laboratory parameters included the urinalysis, hematology, serum chemistry, coagulation and liver function parameters. Clinical significance was determined by the investigator.

   Time frame: Up to Day 72

3. Number of Participants With Clinically Significant Changes in Vital Sign Parameters

   Vital signs measurements included blood pressure, heart rate, and respiration rate, body temperature, pulse oximetry, and weight. Clinical significance was determined by the investigator.

   Time frame: Up to Day 72

4. Number of Participants With Clinically Significant Changes in Physical Examination Parameters

   Physical examination included examination of the following body systems: general appearance, eyes, ears, nose, throat, head and neck, chest and lungs, cardiovascular, abdomen, musculoskeletal, lymphatic, dermatological, neurological, and extremities. Clinical significance was determined by the investigator.

   Time frame: Up to Day 72

5. Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG)

   Changes in ECG data such as heart rate, rhythm, and other clinically significant abnormalities (left ventricular hypertrophy, pathological Q-waves) were measured. Clinical significance was determined by the investigator.

   Time frame: Up to Day 72

6. Change From Baseline in Forced Vital Capacity (FVC) at Day 21

   Spirometry was used to assess FVC. It was used to assess pulmonary breathing mechanics.

   Time frame: Baseline, Day 21

7. Subjective Opiate Withdrawal (SOWS) Total Raw Score

   The SOWS is a self-administered scale for grading opioid withdrawal symptoms and was collected via the study issued e-diary. It consisted of 16 symptoms related to how the participant felt. Each symptom was scored between 0 to 4. The total score ranges between 0 to 64, higher score indicates more severe symptoms.

   Time frame: Up to Day 72

8. Daytime Cough Frequency at Baseline

   Daytime cough was defined as cough that occurs between the time that the participant is a wake in the 24 hours after the digital cough monitor was applied for use. Assessment was done using objective digital cough monitoring. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: At Baseline

9. Percent Change From Baseline in Daytime Cough Frequency at Day 22

   Daytime cough was defined as cough that occurs between the time that the participant is a wake in the 24 hours after the digital cough monitor was applied for use. Assessment was done using objective digital cough monitoring. Percent change in daytime cough frequency (coughs per hour) from baseline was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Day 22

Secondary outcomes

1. Change From Baseline in Daytime Cough Frequency at Day 22

   Daytime cough was defined as cough that occurs between the time that the participant wakes up and the time that the participant goes to bed. Assessment was done using objective digital cough monitoring. The change in daytime cough frequency (coughs per hour) from baseline was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Day 22

2. Percent Change From Baseline in 24-Hour Cough Frequency at Day 22

   Percent change in 24-hour (combined daytime and nighttime) cough frequency (coughs per hour) from baseline was assessed. Assessment was done using objective digital cough monitoring. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Day 22

3. Percent Change From Baseline in Nighttime Cough Frequency at Day 22

   Nighttime cough frequency was intended as the average coughs per hour while the participant was flagged as being asleep. Assessment was done using objective digital cough monitoring. Percent change in cough frequency (coughs per hour) from baseline was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Day 22

4. Mean Change From Baseline in the Evaluating Respiratory Symptoms (E-RS) Diary Cough Subscale at Days 9, 16, and 22

   E-RS daily diary instrument has four separate respiratory symptom domain scales which is a valid, reliable and sensitive measure of four distinct respiratory symptoms. The four domain scales that included cough \[E-RS item 2- How often did you cough today?;score range 0 (not at all)-4 (almost constantly)\], and other items such as breathlessness \[score 0(not at all)-23(severe symptoms)\], sputum \[0(not at all)-8(severe symptoms)\], and chest symptoms \[0(not at all)-12(severe symptoms)\]. The raw totals for the E-RS score and for each of the subscales were converted to a scale range of 0 to 100 (least symptomatic to most symptomatic). A higher score on the scale indicates a more severe grade to the symptom. Negative score indicates improvement in the symptom. The mean change from baseline in the E-RS diary cough scores was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Days 9, 16, and 22

5. Mean Change From Baseline in E-RS Breathlessness Score at Days 9, 16, and 22

   E-RS daily diary instrument has four separate respiratory symptom domain scales which is a valid, reliable and sensitive measure of four distinct respiratory symptoms. The four domain scales included breathlessness \[E-RS items 7 (were you breathless today), 8 (how breathless were you today), 9 (breathlessness doing personal care activities),10 (breathlessness doing indoor activities) \& 11 (breathlessness doing outdoor activities); score =0: not at all) - 23: almost constantly\]. Other items were cough (0: not at all-4: severe), sputum (0: not at all-8: severe), and chest symptoms (0: not at all)-12: severe symptoms). The raw totals for the E-RS score and for subscales were converted to a scale of 0 to 100 (least to most symptoms). Higher score=more severe grade to the symptom. Negative score=improvement in symptom. The mean change from baseline was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Days 9, 16, and 22

6. Mean Change From Baseline in the Cough Severity Numerical Rating Scale (NRS) at Days 8, 15, and 21

   The Cough Severity NRS instrument is a single-dimension 11-point Likert scale ranging from 0 (no cough) to 10 (worst possible cough). Negative score indicates improvement in the symptoms. Participants completed the cough numerical severity rating via the study specific e-diary. The mean change from baseline in the Cough Severity Numerical Rating Scale was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Days 8, 15, and 21

7. Mean Change From Baseline in the 14-item EXAcerbation of Chronic Pulmonary Disease Tool (EXACT) v1.1 e-Diary Tool Total Score at Days 9, 16, and 22

   The EXACT tool is a 14-item Daily Diary Tool Patient-reported outcome (PRO) instrument that was developed to quantify and measure exacerbations of chronic obstructive pulmonary disease (COPD). It provides a total score and subscale scores for breathlessness, cough and sputum, and chest symptoms. The 14 items have interval-level scale ranging between 0 to 100. The total score of each domain of breathlessness, cough and sputum, and chest symptoms ranges from 0 to 100. A higher score indicates a more severe condition. Negative score indicated improvement in the symptoms. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Days 9, 16, and 22

8. Mean Change From Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) Item Bank v1.0 Fatigue Short Form 7a Scale Total Score at Day 21

   The PROMIS Fatigue Short Form 7a is a self-administered Likert-type rating 5-point scale of 7 questions that assess tiredness, exhaustion, energy, fatigue limit, tiredness to think, tiredness impact on hygiene and impact on ability to exercise strenuously over the past 7 days. It consisted of 7 items with each item was scored between 1 to 5. The total score could range between 1 to 35, higher score indicates more severe symptoms. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

   Time frame: Baseline, Day 21

9. Clinical Global Impression of Change (CGI-C) Over Time Measured at Day 21

   The CGI-C is a one-item measure evaluating change from the initiation of treatment on a 7-point scale. It provides an overall clinician-determined summary measure that takes into account all available information, including knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The total score ranges between 0 (very much improved) to 7 (very much worse). The lower scores indicate an improvement in respiratory symptoms.

   Time frame: At Day 21

Baseline characteristics

Study documents

• Study protocol · Dec 14, 2021
• Statistical analysis plan · Jun 8, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No