A Phase 3, Multi-Center, Open-Label Study of a Levonorgestrel-Releasing Intrauterine System for Long-Term, Reversible Contraception
Phase: PHASE3
Conditions: Contraception
Sponsor: Medicines360



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Medicines360 
LNG20 
Clinical Study Protocol 
M360-L1O2 
Walsh T, Grimes D, Frezieres R, Nelson A, Bernstein L, Coulson A, et al. Randomized 
controlled trial of prophylactic antibiotics before insertion of intrauterine devices. Lancet 
1998;35 l: 1005-8. 
Wu JP, Pickle S. Extended use of the intrauterine device: a literature review and 
recommendations for clinical practice. Contraception 2014;89:495-503. 
Version 9.0 
CONFIDENTIAL 
Retrieved from the Medicines360 Veeva EDMS on 21 Sep 2023 by 
Page 96 of 108 

Medicines360 
LNG20 
Protocol Synopsis 
Changed Planned Study Dates 
Planned Study 
Dates, Duration of 
Subject 
Participation, 
Duration of Study 
Center 
Participation, 
Protocol Section 2 
Protocol Synopsis 
Study Design, 
Protocol Section 
3.1, 6.4 
Protocol Synopsis 
Study Design, 
Dosing Regimen, 
Protocol Sections 
3.1, 5, 6.6 
Protocol Synopsis 
Study Design, 
Other Secondary 
Outcome Measures, 
Protocol Sections 
2.2, 3.1, 3.2.3, 
4.4.3, 6.10.3 
Protocol Synopsis 
Key Secondary 
Outcome Measures, 
Statistical Methods, 
Protocol Sections 
3.2.2, 9.1, 9.8 
Added study assessments at Months 102, 108, 1 14, 
120, 121 
Added treatment discontinuation for LNG20 16-35 
year old subjects at Month 121 and for LNG20 16-35 
year old subjects at Month 96 
Levonorgestrel sampling after IUS removal revised to 
start at Month 121 
Added years 8, 9 and 10 to efficacy determination 
Removed requirement for acceptable Pearl Index 
Version 9.0 
CONFIDENTIAL 
Clinical Study Protocol 
M360-L 102 
Extension of the protocol intended duration of use 
from 8 years to 10 years 
Extension of the protocol intended duration of use 
from 8 years to l O years 
Extension of the protocol intended duration of use 
from 8 years to 10 years for LNG20 subjects only. 
Month 121 added to ensure a complete duration of 
use through IO years. Discontinuing LNG20 36-45 
year old enrollment group at 8 years because their 
age at discontinuation will be 43 to 53 years old and 
therefore unlikel to re uire contrace tion. 
Extension of the protocol intended duration of use 
from 8 years to 10 years 
Extension of the protocol intended duration of use 
from 8 years to 10 years 
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Medicines360 
LNG20 
Protocol Synopsis 
Revised cumulative pregnancy rates to be determined 
Other Secondary 
through year 10 
Outcome Measures, Added years 9 and 10 for LNG20 subjects only for 
Protocol Sections 
3.2.3, 9.9 
IUS continuation rates, IUS expulsion rates and IUS 
safety-related removal rates 
Protocol Synopsis 
Revised sample size 
Sample Size, 
Protocol Section 
9.1 
Protocol Section 
Revised approved duration of use for Liletta® from 3 
1.1.1 
to 4 years 
Protocol Section 
Revised Bleeding/Cramping F onn, hemoglobin, 
6.4 
plasma levonorgestrel collection visits and breast 
exam, pelvic exam, Pap testing and STD testing 
schedule 
Protocol Section 
Added study contacts at Months 99, 105, 111 and 
6.5 
117, and revised Bleeding/Cramping Form collection 
visits 
Added contact with LNG20 subjects approaching 
Year 10 discontinuation to notify them of option of 
extending use to 1 O years 
Protocol Section 
Added summary of release rate data of LNG20 
7.1. l 
projected to 10 years 
Protocol Section 
Revised bleeding/cramping form completion duration 
7.12.1 
to 121 months 
Protocol Section 
Increased dropout rate 
9.1 
Version 9.0 
CONFIDENTIAL 
Clinical Study Protocol 
M360-L 102 
Extension of the protocol intended duration of use 
from 8 years to l O years 
Extension of the protocol intended duration of use 
from 8 years to 10 years 
Extension of the protocol intended duration of use 
from 8 years to 10 years with concomitant additional 
subject dropouts 
Liletta (LNG20) approved for extension to 4 years 
of use in 2017 
Extension of the protocol intended duration of use 
from 8 years to 10 years 
Extension of the protocol intended duration of use 
from 8 years to 10 years 
Extension of the protocol intended duration of use 
from 8 years to 10 years 
Provided to assess the risk of pregnancy beyond 8 
years due to extension of the study to l O years 
duration of use 
Extension of the protocol intended duration of use 
from 8 years to IO years 
Extension of the protocol intended duration of use 
from 8 vears to 10 vears 
Page 107 of 108 
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Medicines360 
LNG20 
Protocol Section l 1 
Added references 
Appendix A, 
Revised Schedule of Events 
Schedule of Events 
Version 9.0 
CONFIDENTIAL 
Clinical Study Protocol 
M360-L102 
Additional references provided for Section 7 .1.1 
Additional time points and events were added to 
extend the study to IO years duration of use for 
LNG20 16-35 year olds and discontinue LNG20 36-
45 year olds at 8 years duration of use 
Page 108 of 108 
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