Phase II Study of Oral Nafithromycin in CABP
Sponsor
Wockhardt (Industry)
Overall Status
Completed
CT.gov ID
NCT02903836
Collaborator
ACM (Other)
231
6
3
7.6
38.5
5.1
Study Details
Study Description
Brief Summary
Study to Determine the Safety, Tolerability, Pharmacokinetics and Efficacy of Oral Nafithromycin Versus Oral Moxifloxacin in the Treatment of Community-Acquired Bacterial Pneumonia (CABP) in Adults
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
231 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II, Randomized, Double-Blind, Multicenter, Comparative Study to Determine the Safety, Tolerability, Pharmacokinetics and Efficacy of Oral Nafithromycin Versus Oral Moxifloxacin in the Treatment of Community-Acquired Bacterial Pneumonia (CABP) in Adults
Actual Study Start Date
:
Nov 18, 2016
Actual Primary Completion Date
:
Jul 1, 2017
Actual Study Completion Date
:
Jul 8, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Nafithromycin 800 mg 3 days PO q24h for 3 days; subjects will receive matching placebo , to maintain the blind |
Drug: Nafithromycin 800 mg 3 days
|
| Experimental: Nafithromycin 800 mg 5 days PO q24h for 5 days; subjects will receive matching placebo, to maintain the blind |
Drug: Nafithromycin 800 mg 5 days
|
| Active Comparator: Moxifloxacin 400 mg PO q24h for 7 days;subjects will also receive two nafithromycin placebo tablets PO q24h on Days 1 through Day 7 to maintain the blind |
Drug: Moxifloxacin 400 mg
|
Outcome Measures
Primary Outcome Measures
- Clinical Response in the ITT Population [Day 4 from start of drug administration]
The primary efficacy endpoint was clinical response (response, non-response, or indeterminate) at Day 4, tested in the ITT population. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance
Secondary Outcome Measures
- Clinical Response in the Micro-ITT Population [Day 4 from start of drug administration]
Clinical response (response, non-response, or indeterminate) at Day 4 was also tested in the micro-ITT population as a secondary efficacy endpoint. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Meet the clinical criteria for CABP based on following:
-
Clinical symptoms (new or worsening)
-
Vital sign abnormalities
-
Laboratory abnormalities
-
Radiographic evidence of CABP
-
PORT score
Exclusion Criteria:
-
Subjects with any of the following confirmed or suspected types of pneumonia:
-
Aspiration pneumonia
-
Hospital-acquired bacterial pneumonia (HABP)
-
Healthcare-associated bacterial pneumonia (HCAP)
-
Ventilator-associated bacterial pneumonia (VABP)
-
Pneumonia that may be caused by pathogen(s) resistant to either study drug
-
Receipt of 1 or more dose(s) of a potentially effective systemic antibacterial treatment for treatment of the current CABP
-
Suspected or confirmed non-infectious causes of pulmonary infiltrates
-
Subjects requiring concomitant adjunctive or additional potentially-effective systemic antibacterial treatment for management of CABP
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Empire Clinical Research, LLC | Miami Lakes | Florida | United States | 33016 |
| 2 | A & L Clinical research | Miami | Florida | United States | 33126 |
| 3 | A Plus Research Inc. | Miami | Florida | United States | 33144 |
| 4 | RM Medical Research, Inc. | Miami | Florida | United States | 33175 |
| 5 | HCI Metromedic Walkin Medical Center | Bedford | Massachusetts | United States | 02740-6634 |
| 6 | Health Concepts | Bedford | South Dakota | United States | 57702 |
Sponsors and Collaborators
- Wockhardt
- ACM
Investigators
- Study Director: Ashima Bhatia, MD PDCR, Wockhardt
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Wockhardt
ClinicalTrials.gov Identifier:
NCT02903836
Other Study ID Numbers:
- W-4873-201
First Posted:
Sep 16, 2016
Last Update Posted:
Dec 20, 2019
Last Verified:
Dec 1, 2019
Study Results
Participant Flow
| Recruitment Details | 2 subjects withdrew consent prior to receiving study drug and 7 subjects whose PK results showed no detectable level of either nafithromycin or moxifloxacin hence 9 subjects excluded from the Safety population. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg |
|---|---|---|---|
| Arm/Group Description | PO q24h for 3 days; subjects will receive matching placebo , to maintain the blind Nafithromycin 800 mg 3 days | PO q24h for 5 days; subjects will receive matching placebo, to maintain the blind Nafithromycin 800 mg 5 days | PO q24h for 7 days;subjects will also receive two nafithromycin placebo tablets PO q24h on Days 1 through Day 7 to maintain the blind Moxifloxacin 400 mg |
| Period Title: Overall Study | |||
| STARTED | 74 | 73 | 77 |
| COMPLETED | 71 | 69 | 73 |
| NOT COMPLETED | 3 | 4 | 4 |
Baseline Characteristics
| Arm/Group Title | Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg 7 Days | Total |
|---|---|---|---|---|
| Arm/Group Description | PO q24h for 3 days; subjects will receive matching placebo , to maintain the blind Nafithromycin 800 mg 3 days | PO q24h for 5 days; subjects will receive matching placebo, to maintain the blind Nafithromycin 800 mg 5 days | PO q24h for 7 days;subjects will also receive two nafithromycin placebo tablets PO q24h on Days 1 through Day 7 to maintain the blind Moxifloxacin 400 mg 7 days | Total of all reporting groups |
| Overall Participants | 74 | 73 | 77 | 224 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
57.00
(15.73)
|
54.90
(16.90)
|
56.10
(15.18)
|
56.00
(15.89)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
37
50%
|
32
43.8%
|
35
45.5%
|
104
46.4%
|
| Male |
37
50%
|
41
56.2%
|
42
54.5%
|
120
53.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
3
4.1%
|
2
2.7%
|
8
10.4%
|
13
5.8%
|
| Not Hispanic or Latino |
71
95.9%
|
70
95.9%
|
68
88.3%
|
209
93.3%
|
| Unknown or Not Reported |
0
0%
|
1
1.4%
|
1
1.3%
|
2
0.9%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
2.7%
|
2
2.7%
|
2
2.6%
|
6
2.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
1.4%
|
1
1.3%
|
2
0.9%
|
| Black or African American |
15
20.3%
|
18
24.7%
|
15
19.5%
|
48
21.4%
|
| White |
57
77%
|
52
71.2%
|
59
76.6%
|
168
75%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
4
5.4%
|
4
5.5%
|
8
10.4%
|
16
7.1%
|
| Bulgaria |
14
18.9%
|
16
21.9%
|
11
14.3%
|
41
18.3%
|
| Georgia |
8
10.8%
|
8
11%
|
9
11.7%
|
25
11.2%
|
| Latvia |
4
5.4%
|
1
1.4%
|
4
5.2%
|
9
4%
|
| Romania |
7
9.5%
|
4
5.5%
|
4
5.2%
|
15
6.7%
|
| Serbia |
18
24.3%
|
19
26%
|
21
27.3%
|
58
25.9%
|
| South Africa |
19
25.7%
|
21
28.8%
|
20
26%
|
60
26.8%
|
Outcome Measures
| Title | Clinical Response in the ITT Population |
|---|---|
| Description | The primary efficacy endpoint was clinical response (response, non-response, or indeterminate) at Day 4, tested in the ITT population. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance |
| Time Frame | Day 4 from start of drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg |
|---|---|---|---|
| Arm/Group Description | PO q24h for 3 days; subjects will receive matching placebo , to maintain the blind Nafithromycin 800 mg 3 days | PO q24h for 5 days; subjects will receive matching placebo, to maintain the blind Nafithromycin 800 mg 5 days | PO q24h for 7 days;subjects will also receive two nafithromycin placebo tablets PO q24h on Days 1 through Day 7 to maintain the blind Moxifloxacin 400 mg |
| Measure Participants | 74 | 73 | 77 |
| Count of Participants [Participants] |
68
91.9%
|
65
89%
|
67
87%
|
| Title | Clinical Response in the Micro-ITT Population |
|---|---|
| Description | Clinical response (response, non-response, or indeterminate) at Day 4 was also tested in the micro-ITT population as a secondary efficacy endpoint. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance |
| Time Frame | Day 4 from start of drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| The micro-ITT population included all ITT subjects who had at least one baseline Gram-positive or atypical bacterial pathogen known to cause CABP. |
| Arm/Group Title | Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg |
|---|---|---|---|
| Arm/Group Description | PO q24h for 3 days; subjects will receive matching placebo , to maintain the blind Nafithromycin 800 mg 3 days | PO q24h for 5 days; subjects will receive matching placebo, to maintain the blind Nafithromycin 800 mg 5 days | PO q24h for 7 days;subjects will also receive two nafithromycin placebo tablets PO q24h on Days 1 through Day 7 to maintain the blind Moxifloxacin 400 mg |
| Measure Participants | 22 | 27 | 20 |
| Count of Participants [Participants] |
21
28.4%
|
26
35.6%
|
18
23.4%
|
Adverse Events
| Time Frame | From signing of Informed Consent Form to Follow up Visit (Day 31) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg 7 Days | |||
| Arm/Group Description | PO q24h for 3 days; subjects will receive matching placebo , to maintain the blind Nafithromycin 800 mg 3 days | PO q24h for 5 days; subjects will receive matching placebo, to maintain the blind Nafithromycin 800 mg 5 days | PO q24h for 7 days;subjects will also receive two nafithromycin placebo tablets PO q24h on Days 1 through Day 7 to maintain the blind Moxifloxacin 400 mg 7 days | |||
All Cause Mortality |
||||||
| Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg 7 Days | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/74 (0%) | 0/72 (0%) | 1/76 (1.3%) | |||
Serious Adverse Events |
||||||
| Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg 7 Days | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/74 (1.4%) | 1/72 (1.4%) | 2/76 (2.6%) | |||
| Cardiac disorders | ||||||
| Cor pulmonale | 1/74 (1.4%) | 1 | 0/72 (0%) | 0 | 0/76 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||
| Hypertrophic cardiomyopathy | 1/74 (1.4%) | 1 | 0/72 (0%) | 0 | 0/76 (0%) | 0 |
| Infections and infestations | ||||||
| Urinary tract infection | 0/74 (0%) | 0 | 0/72 (0%) | 0 | 1/76 (1.3%) | 1 |
| Nervous system disorders | ||||||
| Ischemic Stroke | 0/74 (0%) | 0/72 (0%) | 0 | 1/76 (1.3%) | 1 | |
| Epilepsy | 0/74 (0%) | 0 | 0/72 (0%) | 0 | 1/76 (1.3%) | 1 |
| Cerebral ischaemia | 0/74 (0%) | 0 | 1/72 (1.4%) | 1 | 0/76 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Nafithromycin 800 mg 3 Days | Nafithromycin 800 mg 5 Days | Moxifloxacin 400 mg 7 Days | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/74 (14.9%) | 9/72 (12.5%) | 6/76 (7.9%) | |||
| Gastrointestinal disorders | ||||||
| Vomiting | 3/74 (4.1%) | 1/72 (1.4%) | 0/76 (0%) | |||
| Nausea | 3/74 (4.1%) | 5/72 (6.9%) | 2/76 (2.6%) | |||
| Diarrhoea | 2/74 (2.7%) | 2/72 (2.8%) | 3/76 (3.9%) | |||
| Vascular disorders | ||||||
| Hypertension | 3/74 (4.1%) | 1/72 (1.4%) | 2/76 (2.6%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Dr Manishkumar D Shah |
|---|---|
| Organization | Wockhardt |
| Phone | 02226534444 ext 6893 |
| manish.shah@wockhardt.com |
Responsible Party:
Wockhardt
ClinicalTrials.gov Identifier:
NCT02903836
Other Study ID Numbers:
- W-4873-201
First Posted:
Sep 16, 2016
Last Update Posted:
Dec 20, 2019
Last Verified:
Dec 1, 2019