A clinical trial to study the effects of an investigational new drug, ACHN-490 Injection in patients with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP).
- Registration Number
- CTRI/2010/091/000686
- Lead Sponsor
- Achaogen, Inc.7000 Shoreline Court, Suite 372South San Francisco, CA 94080, USA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 240
1. Able to understand and provide written informed consent.
2. Age of ≥ 18 to ≤ 85 years
3. An estimated dry body weight (non-edematous or non-volume
expanded weight) of ≤ 100 kg.
4. Documented* or suspected cUTI/AP with clinical signs and
symptoms as specified below:
a. Presence of a complicated lower tract infection (cUTI),
manifested by at least TWO of the following
i. Fever (oral temperature of > 38.5°C or > 101.3°F), or
elevated WBC (>10,000/mm3, or left shift (> 15%
immature PMNs)
ii. Dysuria
iii. Pyuria (≥ 5 white blood cells (WBCs)/high power field
[hpf] in urine sediment plus positive leukocyte esterase
[LCE] on urinalysis)
iv. Increased frequency
v. Urgency
vi. Lower abdominal pain
AND at least ONE of the following:
i. Indwelling catheter
ii. Urine residual volume of ≥ 100 mL (within the last
6 months) as previously determined by voiding
cystourethrogram (VCUG) or ultrasound or straight
catheterization immediately post void
iii. Neurogenic bladder (excludes dropped bladders without
documented residual volume)
iv. Urinary retention in men due to previously diagnosed
benign prostatic hypertrophy (BPH)
OR:
b. Presence of clinical signs and symptoms of an ascending tract
infection (acute pyelonephritis [AP]), manifested by both fever (oral
temperature of >38.5°C or > 101.5°F; see APPENDIX 8), or
elevated WBC (>10,000/mm3, or left shift (> 15% immature PMNs)
and lower back/flank pain,
AND at least TWO of the following:
i. Costovertebral angle tenderness
ii. Nausea
iii. Chills
iv. Dysuria
v. Pyuria (≥ 5 WBCs/hpf in urine sediment plus positive
LCE on urinalysis)
vi. Increased urinary frequency
vii. Urgency
viii. Vomiting
*Documented cUTI/AP is defined by a positive pre-randomization
urine culture with a defined urinary bacterial pathogen.
5. Expectation that patients with indwelling catheters will have the
catheter removed or replaced (if removal is not clinically
acceptable) before or as soon as possible, but not longer than
12 hours, after randomization.
6. Normal renal function at Screening as estimated by creatinine
7. Women of childbearing potential: negative pregnancy test before
randomization, not breastfeeding, and using a highly effective
method of contraception? for at least one month before
randomization and through the completion of the study.
? A highly effective method of contraception for female patients
includes one of the following: 1) hormonal implants/patch,2)
injectable hormones, 3) oral hormonal contraceptives, 4) prior
bilateral oophorectomy, 5) prior hysterectomy, 6) prior bilateral
tubal ligation,7) intra-uterine device (IUD), 8) approved cervical
ring, 9) condom, 10) true abstinence, if approved by the PI, or 11)
a vasectomized partner.
8. Expectation, in the judgment of the investigator, that the patient will
survive with effective antibiotic therapy and appropriate supportive
care for the anticipated duration of the study.
9. Willing to comply with all the study activities and procedures,
whether in the hospital or after discharge, throughout the duration
of the study.
(1) Patients with any of the following conditions: underlying renal disease (excluding indication cUTI/AP), myasthenia gravis, parkinsonism, or other neuromuscular disorder (2) Severe blood in the urine requiring intervention other than study drug (3) Urinary tract surgery or urinary tract surgery planned during the study period (4) Known non-renal (excluding bacteremia) source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization (5) Signs of severe sepsis (6) Pregnant or breastfeeding women (7) History of epilepsy or known seizure disorder (8) Receipt of disulfiram (9) Receipt of any investigational medication during the last month prior to randomization (10) Prior exposure to ACHN-490 Injection (11) Treatment with another antibiotic within 48 hours prior to randomization (12) Treatment with fluoroquinolone or bladder irrigation (13) Known history of human immunodeficiency virus (HIV) infection and current or previous CD4 count < 200/mm3 (14) Presence of immunodeficiency or an immunocompromised condition and use of systemic corticosteroids (15) Presence of neutropenia (16) History of hearing loss with onset before the age of 40 years (16) At risk for serious drug interactions because of concomitant medications [e.g., class IA (e.g., quinidine, procainamide, or Class III (e.g, amiodarone, sotalol)antiarrhythmic agents] (17) A QTc (Bazett's)> 440 msec (18) Known hypersensitivity to ACHN-490 Injection, and other aminoglycosides, levofloxacin, other fluoroquinolone antibiotics (19) An employee of the Investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member of the employee or the Investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Microbiological eradication in modified intent to treat (MITT) population and microbiologically evaluable (ME) populationTimepoint: Test-of-Cure (TOC) visit (Day 12)
- Secondary Outcome Measures
Name Time Method Clinical cure (Investigator?s and Sponsor?s assessment)Timepoint: Throughout the study, up to Day 12