PMID- 37725274
OWN - NLM
STAT- MEDLINE
DCOM- 20240113
LR  - 20240113
IS  - 1573-2584 (Electronic)
IS  - 0301-1623 (Print)
IS  - 0301-1623 (Linking)
VI  - 56
IP  - 1
DP  - 2024 Jan
TI  - Intravesical liposomal tacrolimus for hemorrhagic cystitis: a phase 2a 
      multicenter dose-escalation study.
PG  - 87-96
LID - 10.1007/s11255-023-03783-y [doi]
AB  - BACKGROUND: Hemorrhagic cystitis (HC) is an inflammatory disease of the bladder 
      with sustained hematuria for which there is currently no approved drug treatment. 
      We evaluated a liposomal tacrolimus preparation (LP-10) in patients with 
      refractory moderate to severe sterile HC. METHODS: This phase 2a dose-escalation 
      study assessed the safety and efficacy of up to 2 intravesical instillations of 
      LP-10 (2, 4, or 8 mg tacrolimus) in 13 patients with HC. Primary efficacy 
      outcomes were changes from baseline in the number of bleeding sites on 
      cystoscopy, microscopic urine analysis for red blood cells (RBCs), and hematuria 
      on dipstick. Additional efficacy measures included urinary incontinence, 
      frequency, and urgency on a 3-day diary and cystoscopy global response assessment 
      (GRA). Blood samples for pharmacokinetic (PK) assessment were obtained in all 
      patients. RESULTS: Intravesical LP-10 was well tolerated, with no 
      treatment-related severe or serious adverse events (AEs) and only 3 drug-related 
      AEs (artificial urinary sphincter malfunction, dysuria, and bladder spasms). 
      LP-10 blood levels showed short durations of minimal systemic uptake. Treatment 
      resulted in significant improvements in bleeding on cystoscopy, RBC counts in 
      urine, hematuria on dipstick, and urinary incontinence. Bleeding on cystoscopy 
      and urinary incontinence showed dose-dependent improvements that were more 
      pronounced in the 4 mg and 8 mg dose groups. All dose groups showed a significant 
      improvement in cystoscopy GRA. CONCLUSION: LP-10 was well tolerated, with 
      clinically relevant efficacy seen in improvements in cystoscopic bleeding, 
      hematuria, and urinary incontinence. The benefit-risk profile supports the 
      further clinical development of LP-10 at a tacrolimus dose of 4 mg.
CI  - (c) 2023. The Author(s).
FAU - Hafron, Jason
AU  - Hafron J
AD  - Michigan Institute of Urology, Troy, MI, USA.
FAU - Breyer, Benjamin N
AU  - Breyer BN
AD  - University of California, San Francisco, San Francisco, CA, USA.
FAU - Joshi, Shreyas
AU  - Joshi S
AD  - Emory University, Atlanta, GA, USA.
FAU - Smith, Christopher
AU  - Smith C
AD  - Baylor College of Medicine, Houston, TX, USA.
FAU - Kaufman, Melissa R
AU  - Kaufman MR
AD  - Vanderbilt University, Nashville, TN, USA.
FAU - Okonski, Janet
AU  - Okonski J
AD  - Lipella Pharmaceuticals, Inc, Pittsburgh, PA, USA.
FAU - Chancellor, Michael B
AU  - Chancellor MB
AUID- ORCID: 0000-0001-9480-8972
AD  - Lipella Pharmaceuticals, Inc, Pittsburgh, PA, USA. 
      michael.chancellor@lipella.com.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Multicenter Study
DEP - 20230919
PL  - Netherlands
TA  - Int Urol Nephrol
JT  - International urology and nephrology
JID - 0262521
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Humans
MH  - Administration, Intravesical
MH  - *Cystitis/drug therapy
MH  - *Cystitis, Hemorrhagic
MH  - Hematuria/drug therapy/etiology
MH  - Hemorrhage/etiology
MH  - Tacrolimus/therapeutic use
MH  - Urinary Bladder
MH  - *Urinary Incontinence
PMC - PMC10776496
OTO - NOTNLM
OT  - Bladder
OT  - Hemorrhagic cystitis
OT  - Intravesical instillation
OT  - Topical liposomal tacrolimus
COIS- JO and MC are affiliated with Lipella Pharmaceuticals as employees. All other 
      authors have no competing interests to declare, except for their roles as trial 
      investigators.
EDAT- 2023/09/19 17:42
MHDA- 2024/01/10 06:41
PMCR- 2023/09/19
CRDT- 2023/09/19 11:11
PHST- 2023/08/16 00:00 [received]
PHST- 2023/09/01 00:00 [accepted]
PHST- 2024/01/10 06:41 [medline]
PHST- 2023/09/19 17:42 [pubmed]
PHST- 2023/09/19 11:11 [entrez]
PHST- 2023/09/19 00:00 [pmc-release]
AID - 10.1007/s11255-023-03783-y [pii]
AID - 3783 [pii]
AID - 10.1007/s11255-023-03783-y [doi]
PST - ppublish
SO  - Int Urol Nephrol. 2024 Jan;56(1):87-96. doi: 10.1007/s11255-023-03783-y. Epub 
      2023 Sep 19.