COPD, Bronchiectasis
Conditions
Brief summary
Patients with a respiratory disease are at higher risk of poor outcomes due to worsening of symptoms caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and other respiratory infections. New therapies are needed for treating high risk patients at early stages of an infection. This study will assess the safety, tolerability and feasibility of using an inhaled nitric oxide generating solution, RESP301, as a self-administered treatment following flare-up of symptoms. RESP301 is a liquid solution which produces nitric oxide in the lungs when inhaled using a nebuliser. The components of RESP301 are already used in clinical practice and inhaled nitric oxide is used as a treatment for newborns and patients with Chronic Obstructive Pulmonary Disease (COPD). In a laboratory setting, RESP301 has been shown to be effective against respiratory viruses, including SARS-CoV-2. This study will first determine the maximum tolerated dose of RESP301 in up to 48 adult patients with COPD or bronchiectasis in the United Kingdom (UK) (Part 1a; Dose Finding Phase). Once the Maximum Tolerated Dose (MTD) has been determined in Part 1a, a cohort of 8 patients will be recruited and RESP301 administered at the MTD but these patients will in addition receive a single dose of a short acting bronchodilator 10 minutes preceding administration of RESP301. After completion of Part 1, approximately 150 patients will be recruited into Part 2 of the trial (Expansion Phase). A minimum of 50 participants will receive a test dose of RESP301 during a screening visit. Response to the test dose will be monitored. Participants who tolerate the test dose will continue in the study and should contact the study team if they experience exacerbation symptoms in the next 52 weeks. Following a call with the site team to discuss symptoms, participants will receive RESP301 delivered to their home to self-administer for 7 days. The study duration for each participant will be at most 57 weeks, including the study visit and monthly calls. Participants who start the course of study treatment, will receive daily calls during the treatment period and will also be followed up after they complete the treatment.
Interventions
DRUGRESP301
A single RESP301 dose administered at a study site to assess tolerability. In patients who experience a flare-up during the study period, self-administered RESP301 treatment for 7 days, 3 times a day.
Sponsors
Thirty Respiratory Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Part 1a: Dose Finding Phase Up to 48 eligible participants will be administered single ascending doses of RESP301 to determine the maximum tolerated dose, according to the following schedule: * 8 participants to receive RESP301 at a dose of 1 ml * 8 participants to receive RESP301 at a dose of 2 ml * 8 participants to receive RESP301 at a dose of 3 ml * 8 participants to receive RESP301 at a dose of 4 ml * 8 participants to receive RESP301 at a dose of 5 ml * 8 participants to receive RESP301 at a dose of 6 ml Part 1b: Concomitant Medication Expansion Phase • 8 participants to receive RESP301 at MTD with short-acting bronchodilator administered 10min prior to RESP301 Part 2: Expansion Phase A minimum of 150 patients will be enrolled in to the Expansion Phase. These may include eligible participants from Part 1.
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female of non-childbearing potential or male ≥35 years of age, at the time of signing the informed consent 2. Able and willing to provide informed consent 3. Spirometry-confirmed diagnosis of COPD (FEV1/FVC\<0.7 post-bronchodilator) or computerised tomography (CT) proven bronchiectasis 4. Part 1 only: FEV1 ≥50% predicted at screen 1 (i.e. FEV1 prior to any in-clinic administered short acting bronchodilator)
Exclusion criteria
1. Unable to safely use a nebuliser as required by the study according to Investigator's opinion 2. Severe COPD or bronchiectasis defined as FEV1 \<20% or requiring non-invasive ventilation 3. History of methaemoglobinaemia 4. Baseline methaemoglobin concentration (using fingertip sensor) \> 2% 5. Uncontrolled or severe asthma or history of severe bronchospasm 6. Presence of tracheostomy/inability to provide spirometry or contraindication for performing spirometry 7. Allergy to any of the components of the study intervention 8. Participation in other clinical investigations utilising investigational treatment within the last 30 days / 5 half lives whichever is longer 9. Deemed unlikely to be able to adhere to protocol in view of investigator 10. Any subject who in the opinion of the investigator would not be best served by participating in this clinical trial 11. Any unstable, uncontrolled or severe medical condition which in the opinion of the investigator would make the patient unsuitable for the trial 12. Participant lives at home with no other adults in the household (Part 2 only) 13. On long-term non-invasive ventilation and/or at higher risk of bronchospasm 14. Prescribed Nitric Oxide donating agent (Nitroprusside, Isosorbide dinitrate, Isosorbide mononitrate, Naproxcinod, Molsidomine and Linsidomine) 15. Female of childbearing potential 16. Clinical diagnosis of COPD but Screening Visit spirometry at study centre excludes COPD (i.e. FEV1/FVC post bronchodilator ratio is not \<0.7)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | Screening Visit | Defined as percentage of participants able to tolerate the test dose, i.e. able to complete the test dose without any of the following: * Troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient * methaemoglobin \>5% during or \>3% post dose (60 mins) * any treatment-related AE that led to participant not being able to complete the test dose * \>20% reduction in FEV1 pre dose to post dose at 60min if additionally reporting troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient |
| Feasibility of Self-administering RESP301 Treatment in Terms of Commencing Treatment | 1 day | Defined as percentage of patients who, having experienced and correctly reported an exacerbation, commence self-administration of the treatment on the day the treatment is delivered |
| Feasibility of Self-administering RESP301 Treatment in Terms of Treatment Compliance | 7 days | For those participants commencing self-administration of RESP301, the percentage of total doses taken |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination) | Defined as total counts and cumulative incidence of Suspected Unexpected Serious Adverse Reactions (SUSARs) |
| Safety of RESP301 in Terms of Treatment-related AEs | Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination) | Defined as total counts and cumulative incidence of treatment-related AEs |
| Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 7 | 7 days | Defined as percentage of participants recovered by Day 7 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than usual) |
| Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 14 | 7 days | Defined as percentage of participants recovered by Day 14 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than usual) |
| Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | Screening Visit | Defined as percentage of participants able to tolerate the test dose, i.e. able to complete the test dose without any of the following: * Troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient * methaemoglobin \>5% during or \>3% post dose (60 mins) * any treatment-related AE that led to participant not being able to complete the test dose, and/or be suitable to be enrolled into the dormant phase in the Investigator's opinion * for the first 50 patients who will undergo pre spirometry, \>20% reduction in FEV1 from pre test dose to post test dose with symptoms (patients with \>20% reduction in FEV1 without symptoms would be offered the option to continue in the study) |
| Efficacy of RESP301 in Terms of Preventing Exacerbation-related Hospitalisation and/or Death | 7 days | Number of patients treated with RESP301 that experience exacerbation-related hospitalisation and/or death |
| Efficacy of RESP301 in Terms of Patient-reported Symptoms | 7 days | Change in Clinical COPD Questionnaire (CCQ) score from Day 1 to Day 7, where the minimum score is 0 (very good health status) and maximum score is 6 (extremely poor health status) |
| Feasibility of Self-administering RESP301 Treatment in Terms of Receiving Treatment | 2 days | Defined as percentage of patients who, having experienced and correctly reported an exacerbation, receive the treatment within 48 hours of reporting their exacerbation |
| Efficacy of RESP301 in Terms of Time to Recovery | 21 days | Defined as days to recovery, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than Defined as percentage of participants recovered by Day 14 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than usual) |
| Safety of RESP301 in Terms of Treatment Emergent Adverse Events | Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination) | Defined as total counts and cumulative incidence of Treatment Emergent Adverse Events (TEAEs) |
| Safety of RESP301 in Terms of Serious Adverse Events | Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination) | Defined as total counts and cumulative incidence of Serious Adverse Events (SAEs) |
Countries
United Kingdom
Participant flow
Pre-assignment details
total 13 participants enrolled in Part 1A and 10 participants were enrolled in more than one cohort
Participants by arm
| Arm | Count |
|---|---|
| Part 0 Patients who were enrolled under protocol version 3.0 | 4 |
| Part 1A Participants were administered single ascending dose of RESP301 from 1ml to 6ml in the clinic on Day 1, with a follow up safety phone call being conducted on the morning of Day 2 to check for any adverse events. | 13 |
| Part 1B Participants were administered short-acting inhaled bronchodilator (2 inhalations of Ventolin - 100mcg per inhalation) through a spacer device 10 minutes before receiving RESP301 and a single dose of 6ml RESP301 (MTD) in the clinic on Day 1, with a follow up safety phone call being conducted on the morning of Day 2 to check for any adverse events. | 8 |
| Part 2 Participants were administered a single test dose of RESP301 at the RTD of 4 mL. if tolerated and symptoms of exacerbation developed, eligible participants were to self-administer RESP301 TID for 7 days at the RTD. | 16 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part 0 (Protocol Version 3.0) | Discontinued | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 | Discontinued | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 63 |
Baseline characteristics
| Characteristic | Total | Part 0 | Part 1A | Part 1B | Part 2 |
|---|---|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 7.08 | 67.5 years STANDARD_DEVIATION 5.07 | 68.2 years STANDARD_DEVIATION 6.11 | 67.6 years STANDARD_DEVIATION 4.78 | 65.3 years STANDARD_DEVIATION 9.13 |
| Body Mass Index | 29.783 kg/m² STANDARD_DEVIATION 5.7503 | 32.650 kg/m² STANDARD_DEVIATION 8.6157 | 27.954 kg/m² STANDARD_DEVIATION 3.5671 | 30.600 kg/m² STANDARD_DEVIATION 2.8894 | 30.144 kg/m² STANDARD_DEVIATION 7.3258 |
| Height | 1.659 m STANDARD_DEVIATION 0.0981 | 1.663 m STANDARD_DEVIATION 0.0608 | 1.648 m STANDARD_DEVIATION 0.1049 | 1.664 m STANDARD_DEVIATION 0.1119 | 1.664 m STANDARD_DEVIATION 0.1007 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 4 Participants | 13 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 23 Participants | 2 Participants | 7 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 18 Participants | 2 Participants | 6 Participants | 4 Participants | 6 Participants |
| Smoking status Current smoker | 10 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants |
| Smoking status Former smoker | 29 Participants | 2 Participants | 10 Participants | 6 Participants | 11 Participants |
| Smoking status Never smoked | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Weight | 81.93 kg STANDARD_DEVIATION 16.207 | 89.53 kg STANDARD_DEVIATION 20.128 | 75.90 kg STANDARD_DEVIATION 10.992 | 85.19 kg STANDARD_DEVIATION 14.75 | 83.31 kg STANDARD_DEVIATION 19.178 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 8 | 0 / 16 |
| other Total, other adverse events | 4 / 4 | 4 / 8 | 4 / 8 | 1 / 8 | 5 / 8 | 5 / 8 | 4 / 6 | 6 / 8 | 5 / 16 |
| serious Total, serious adverse events | 0 / 4 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 6 | 1 / 8 | 4 / 16 |
Outcome results
Primary
Feasibility of Self-administering RESP301 Treatment in Terms of Commencing Treatment
Defined as percentage of patients who, having experienced and correctly reported an exacerbation, commence self-administration of the treatment on the day the treatment is delivered
Time frame: 1 day
Population: Due to early termination of the study, no participants entered the Treatment Period of Part 2, and therefore no feasibility of self administering RESP301 data was collected.
Primary
Feasibility of Self-administering RESP301 Treatment in Terms of Treatment Compliance
For those participants commencing self-administration of RESP301, the percentage of total doses taken
Time frame: 7 days
Population: Due to early termination of the study, no participants entered the Treatment Period of Part 2, and therefore no feasibility of self administering RESP301 data was collected.
Primary
Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1
Defined as percentage of participants able to tolerate the test dose, i.e. able to complete the test dose without any of the following: * Troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient * methaemoglobin \>5% during or \>3% post dose (60 mins) * any treatment-related AE that led to participant not being able to complete the test dose * \>20% reduction in FEV1 pre dose to post dose at 60min if additionally reporting troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient
Time frame: Screening Visit
Population: participants who received at least one dose of RESP301
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD-1ml | Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | 8 Participants |
| SAD - 2ml | Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | 8 Participants |
| SAD - 3ml | Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | 8 Participants |
| SAD - 4ml | Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | 8 Participants |
| SAD - 5ml | Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | 8 Participants |
| SAD - 6ml | Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | 6 Participants |
| MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA | Proportion of Patients Tolerating RESP301 at Each Dose Level in Part 1 | 8 Participants |
Secondary
Efficacy of RESP301 in Terms of Patient-reported Symptoms
Change in Clinical COPD Questionnaire (CCQ) score from Day 1 to Day 7, where the minimum score is 0 (very good health status) and maximum score is 6 (extremely poor health status)
Time frame: 7 days
Population: Due to early termination of the study, no participants entered the Treatment Period of Part 2, and therefore no efficacy data was collected.
Secondary
Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 14
Defined as percentage of participants recovered by Day 14 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than usual)
Time frame: 7 days
Population: Due to early termination of the study, data were not collected and efficacy could not be analysed
Secondary
Efficacy of RESP301 in Terms of Percentage of Patients Recovered by Day 7
Defined as percentage of participants recovered by Day 7 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than usual)
Time frame: 7 days
Population: Due to early termination of the study, no participants entered the Treatment Period of Part 2, and therefore no efficacy data was collected.
Secondary
Efficacy of RESP301 in Terms of Preventing Exacerbation-related Hospitalisation and/or Death
Number of patients treated with RESP301 that experience exacerbation-related hospitalisation and/or death
Time frame: 7 days
Population: Due to early termination of the study, no participants entered the Treatment Period of Part 2, and therefore no efficacy data was collected.
Secondary
Efficacy of RESP301 in Terms of Time to Recovery
Defined as days to recovery, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than Defined as percentage of participants recovered by Day 14 post starting treatment, where recovery is defined as patient feels all their symptoms are back to their usual baseline (all symptom Visual Analogue Scores are 0 on a scale from 0 to 10, where 0 is same as usual and 10 is much more than usual)
Time frame: 21 days
Population: Due to early termination of the study, no participants entered the Treatment Period of Part 2, and therefore no efficacy data was collected.
Secondary
Feasibility of Self-administering RESP301 Treatment in Terms of Receiving Treatment
Defined as percentage of patients who, having experienced and correctly reported an exacerbation, receive the treatment within 48 hours of reporting their exacerbation
Time frame: 2 days
Population: Due to early termination of the study, no participants entered the Treatment Period of Part 2, and therefore no feasibility of self administering RESP301 data was collected.
Secondary
Safety of RESP301 in Terms of Serious Adverse Events
Defined as total counts and cumulative incidence of Serious Adverse Events (SAEs)
Time frame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
Population: all participants who consented to the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD-1ml | Safety of RESP301 in Terms of Serious Adverse Events | 0 # Events |
| SAD - 2ml | Safety of RESP301 in Terms of Serious Adverse Events | 0 # Events |
| SAD - 3ml | Safety of RESP301 in Terms of Serious Adverse Events | 0 # Events |
| SAD - 4ml | Safety of RESP301 in Terms of Serious Adverse Events | 0 # Events |
| SAD - 5ml | Safety of RESP301 in Terms of Serious Adverse Events | 0 # Events |
| SAD - 6ml | Safety of RESP301 in Terms of Serious Adverse Events | 0 # Events |
| MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA | Safety of RESP301 in Terms of Serious Adverse Events | 0 # Events |
| RTD - 4ml | Safety of RESP301 in Terms of Serious Adverse Events | 6 # Events |
Secondary
Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions
Defined as total counts and cumulative incidence of Suspected Unexpected Serious Adverse Reactions (SUSARs)
Time frame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
Population: participants who received at least one dose of RESP301.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD-1ml | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 0 # Events |
| SAD - 2ml | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 0 # Events |
| SAD - 3ml | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 0 # Events |
| SAD - 4ml | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 0 # Events |
| SAD - 5ml | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 0 # Events |
| SAD - 6ml | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 0 # Events |
| MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 0 # Events |
| RTD - 4ml | Safety of RESP301 in Terms of Suspected Unexpected Serious Adverse Reactions | 1 # Events |
Secondary
Safety of RESP301 in Terms of Treatment Emergent Adverse Events
Defined as total counts and cumulative incidence of Treatment Emergent Adverse Events (TEAEs)
Time frame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
Population: all participants who consented to the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD-1ml | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 4 # Events |
| SAD - 2ml | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 7 # Events |
| SAD - 3ml | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 3 # Events |
| SAD - 4ml | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 8 # Events |
| SAD - 5ml | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 10 # Events |
| SAD - 6ml | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 13 # Events |
| MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 13 # Events |
| RTD - 4ml | Safety of RESP301 in Terms of Treatment Emergent Adverse Events | 16 # Events |
Secondary
Safety of RESP301 in Terms of Treatment-related AEs
Defined as total counts and cumulative incidence of treatment-related AEs
Time frame: Parts 1A/1B: Screening/dosing period 1-2 days + Follow-up period 1 day. Part 2: Screening period 1-2days (Participants did not enter the treatment phase due to early study termination)
Population: participants who received at least one dose of RESP301.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD-1ml | Safety of RESP301 in Terms of Treatment-related AEs | 4 # Events |
| SAD - 2ml | Safety of RESP301 in Terms of Treatment-related AEs | 4 # Events |
| SAD - 3ml | Safety of RESP301 in Terms of Treatment-related AEs | 2 # Events |
| SAD - 4ml | Safety of RESP301 in Terms of Treatment-related AEs | 7 # Events |
| SAD - 5ml | Safety of RESP301 in Terms of Treatment-related AEs | 8 # Events |
| SAD - 6ml | Safety of RESP301 in Terms of Treatment-related AEs | 12 # Events |
| MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA | Safety of RESP301 in Terms of Treatment-related AEs | 12 # Events |
| RTD - 4ml | Safety of RESP301 in Terms of Treatment-related AEs | 16 # Events |
Secondary
Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2)
Defined as percentage of participants able to tolerate the test dose, i.e. able to complete the test dose without any of the following: * Troublesome cough, chest pain or tightness, bronchospasm or dyspnoea that is deemed unacceptable by the patient * methaemoglobin \>5% during or \>3% post dose (60 mins) * any treatment-related AE that led to participant not being able to complete the test dose, and/or be suitable to be enrolled into the dormant phase in the Investigator's opinion * for the first 50 patients who will undergo pre spirometry, \>20% reduction in FEV1 from pre test dose to post test dose with symptoms (patients with \>20% reduction in FEV1 without symptoms would be offered the option to continue in the study)
Time frame: Screening Visit
Population: participants who received at least one dose of RESP301.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD-1ml | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 8 Participants |
| SAD - 2ml | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 8 Participants |
| SAD - 3ml | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 8 Participants |
| SAD - 4ml | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 8 Participants |
| SAD - 5ml | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 8 Participants |
| SAD - 6ml | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 4 Participants |
| MTD 6ml +SABA MTD 6ml +SABA MTD 6ml +SABA | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 7 Participants |
| RTD - 4ml | Tolerability of RESP301 (in Part 1a, Part 1b, and Part 2) | 12 Participants |