| Primary | Treatment Emergent Adverse Events (TEAEs) up to Day 672 | Treatment emergent adverse events including serious adverse events (SAE) and adverse events (AE) leading to permanent discontinuation of study drug | | Posted | | Count of Participants | | Participants | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
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| | | Title | Denominators | Categories |
|---|
| Patients with ≥1 treatment-emergent AE | | | | Patients with ≥ 1 serious AE | | | | Patients with ≥1 AE leading to discontinuation | | |
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| Primary | Laboratory Abnormalities up to Day 672 |
- Number of Subjects with Grade 3 or Higher Abnormalities in Clinical Laboratory Values
- Number of Subjects with Grade 3 or Higher Hematology Laboratory Value Abnormalities
- Number of Subjects with Grade 3 or Higher Chemistry Laboratory Value Abnormalities
| | Posted | | Count of Participants | | Participants | | Baseline, Day 377 and Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
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| Primary | Acute Tolerability as Measured by Pulmonary Function Test (PFT) Changes Pre to Post Dose | Number of Subjects with a >15% in Decline in Forced Expiratory Volume in 1 Second (FEV1) From Predose to Postdose | Safety Population Patients with missing values were excluded. | Posted | | Count of Participants | | Participants | | Day 1, Day 84, Day 196, Day 281, Day 337, Day 449, Day 532 and Day 644 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
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| Primary | Respiratory Rate: Change From Baseline to Day 672 | Respiratory rate was recorded at every visit as per standard practice at each investigational site. | Safety Population Patients with missing data were excluded. | Posted | | Mean | Standard Deviation | breaths per minute | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
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| Primary | Heart Rate: Change From Baseline From Day 672 | Pulse rate (after at least 5-minute rest) was recorded at every visit as per standard practice at each investigational site. | Safety Population Patients with missing data were excluded. | Posted | | Mean | Standard Deviation | beats/min | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Primary | Systolic BP: Change From Baseline at Day 672 | Sitting blood pressure was recorded at every visit as per standard practice at each investigational site. | Safety Population Patients with missing data were excluded. | Posted | | Mean | Standard Deviation | mmHg | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Primary | Diastolic BP: Change From Baseline at Day 672 | Sitting blood pressure was recorded at every visit as per standard practice at each investigational site. | Safety Population Patients with missing data were excluded. | Posted | | Mean | Standard Deviation | mmHg | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Primary | Body Temperature: Change From Baseline at Day 672 | Body temperature was recorded at every visit as per standard practice at each investigational site. | Safety Population Patients with missing data were excluded. | Posted | | Mean | Standard Deviation | Degrees Celcius | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Primary | Oxygen Saturation: Change From Baseline at Day 672 | Change in oxygen saturation as measured with pulse oximetry was performed via finger probes placed on the extremity opposite arterial lines and noninvasive blood pressure monitoring devices so that pulsatile flow was not interrupted. | Safety Population Patients with missing data were excluded. | Posted | | Mean | Standard Deviation | Percent of Hemoglobin | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI once a day (QD) via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
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| Primary | Minimum Inhibitory Concentrations (MICs) for Pseudomonas Aeruginosa (Pa) and Burkholderia Species From Day 1 to Days 169, 337, 505 and 672 | Sputum was cultured for quantitative microbiological evaluation of Pa and Burkholderia species in designated regional central microbiology laboratories. A standard microbiology protocol was used for Pa culture and identification for each morphologically distinct Pa phenotype. Although planned in the Statistical Analysis Plan (SAP), MICs of amikacin Burkholderia species were not determined due to the small number of isolates with Burkholderia. In addition, susceptibility testing of isolates of Pa and Burkholderia species against a panel of commonly used antipseudomonal antibiotics was planned but was not performed. The results of the following analyses for Pa isolates are presented.
- Frequency of MIC of Amikacin
- Frequency of MIC of Tobramycin
MIC50: lowest concentration of the antibiotic at which 50 % of the isolates were inhibited. | Safety Population Patients with missing data were excluded. | Posted | | Median | Full Range | µg/mL | | Day 1, Day 169, Day 337, Day 505 and Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Primary | Evaluation of Audiology | Hearing was evaluated using air conduction [AC]. Bone conduction was required if the AC testing demonstrated a decrease of >20 decibels [dB]. Hearing loss was categorized using Common Terminology Criteria for Adverse Events as follows: GRADE 1 (best): Adults [A] on a Monitoring Program [MP]: Threshold shift of 15-25 dB; Pediatric [P]: Threshold shift >20 dB at 8 kilohertz (kHz). GRADE 2: [A] on a MP: Threshold shift of >25 dB; [A] not enrolled in MP: hearing loss; hearing aid/intervention not indicated; [P]: Threshold shift >20 dB at 4 kHz and above. GRADE 3: [A] enrolled in MP: Threshold shift of >25 dB; therapeutic intervention indicated; [A]: Not enrolled in MP: hearing aid/intervention; [P]: therapeutic intervention, including hearing aids: Threshold shift >20 dB at 3 kHz and above; additional speech-language related services. GRADE 4 (worst): [A]: Profound bilateral hearing loss; non-serviceable hearing; [P]: cochlear implant & additional speech-language related services. | | Posted | | Count of Participants | | Participants | | Day 337 and Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Primary | Change in Serum Creatinine Throughout the Study |
- Common Terminology Criteria for Adverse Events (CTCAE) Grade 1: > ULN-1.5 × ULN
- CTCAE Grade 2: > 1.5 × ULN to 3.0 x ULN
| | Posted | | Count of Participants | | Participants | | Baseline, Day 337 and Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Secondary | Percent Change in FEV1 Throughout the Study | Percent Change From Baseline in Predose FEV1 | modified intention to treat (mITT) population | Posted | | Mean | Standard Deviation | Percent (%) change | | Baseline, Day 337 and Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Secondary | Number of Subjects Experiencing a Protocol Defined Pulmonary Exacerbation | For number of subjects to first protocol-defined pulmonary exacerbation, follow-up time began at the first dose of study drug (Day 1) and ended no later than Day 700 (28-day follow up). | | Posted | | Number | | participants | | From Study Initiation up to Day 700 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
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| Secondary | Number of Subjects Initiating Treatment. | The number of subjects initiating antipseudomonal therapy for protocol-defined pulmonary exacerbation confirmed by the investigator, and for investigator-defined pulmonary exacerbation were summarized. The data presented below is the Frequency of Systemic or Inhaled Antipseudomonal Therapy for Protocol-defined Pulmonary Exacerbations Confirmed by Investigator - Time to First Use of Any New Antibiotic Treatment, Censoring at Date of Last Contact | | Posted | | Count of Participants | | Participants | | From Study Initiation up to Day 672 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
|
| |
| Secondary | Number of Participants Who Received Antipseudomonal Antibiotic Treatment for Protocol Defined Pulmonary Exacerbation | | | Posted | | Count of Participants | | Participants | | From Study Initiation up to Day 700 | | | | ID | Title | Description |
|---|
| OG000 | LAI 590 mg QD | 590 mg LAI QD via a PARI Investigational eFlow® Nebulizer System (eFlow®) for 28 days followed by a 28-day off-treatment period. This cycle (28 days on treatment, 28 days off treatment) was to be repeated for up to 12 cycles, divided into 2 periods of 6 cycles each (approximately 12 months each). Liposomal amikacin for inhalation: - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
- Administration time is approximately 13 minutes.
- Liposomal amikacin for inhalation will be administered in two consecutive extension periods, each consisting of 6 cycles for a total of 12 cycles. Each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
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