PMID- 28972192
OWN - NLM
STAT- MEDLINE
DCOM- 20171102
LR  - 20220310
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 89
IP  - 17
DP  - 2017 Oct 24
TI  - A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular 
      dystrophy.
PG  - 1811-1820
LID - 10.1212/WNL.0000000000004570 [doi]
AB  - OBJECTIVE: To conduct a randomized trial to test the primary hypothesis that 
      once-daily tadalafil, administered orally for 48 weeks, lessens the decline in 
      ambulatory ability in boys with Duchenne muscular dystrophy (DMD). METHODS: Three 
      hundred thirty-one participants with DMD 7 to 14 years of age taking 
      glucocorticoids were randomized to tadalafil 0.3 mg.kg(-1).d(-1), tadalafil 0.6 
      mg.kg(-1).d(-1), or placebo. The primary efficacy measure was 6-minute walk 
      distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star 
      Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) 
      was a prespecified exploratory outcome. RESULTS: Tadalafil had no effect on the 
      primary outcome: 48-week declines in 6MWD were 51.0 +/- 9.3 m with placebo, 64.7 +/- 
      9.8 m with low-dose tadalafil (p = 0.307 vs placebo), and 59.1 +/- 9.4 m with 
      high-dose tadalafil (p = 0.538 vs placebo). Tadalafil also had no effect on 
      secondary outcomes. In boys >10 years of age, total PUL score and shoulder 
      subscore declined less with low-dose tadalafil than placebo. Adverse events were 
      consistent with the known safety profile of tadalafil and the DMD disease state. 
      CONCLUSIONS: Tadalafil did not lessen the decline in ambulatory ability in boys 
      with DMD. Further studies should be considered to confirm the 
      hypothesis-generating upper limb data and to determine whether ambulatory decline 
      can be slowed by initiation of tadalafil before 7 years of age. CLINICALTRIALSGOV 
      IDENTIFIER: NCT01865084. CLASSIFICATION OF EVIDENCE: This study provides Class I 
      evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old 
      boys with Duchenne muscular dystrophy.
CI  - Copyright (c) 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Victor, Ronald G
AU  - Victor RG
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN. Ronald.victor@cshs.org.
FAU - Sweeney, H Lee
AU  - Sweeney HL
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Finkel, Richard
AU  - Finkel R
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - McDonald, Craig M
AU  - McDonald CM
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Byrne, Barry
AU  - Byrne B
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Eagle, Michelle
AU  - Eagle M
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Goemans, Nathalie
AU  - Goemans N
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Vandenborne, Krista
AU  - Vandenborne K
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Dubrovsky, Alberto L
AU  - Dubrovsky AL
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Topaloglu, Haluk
AU  - Topaloglu H
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Miceli, M Carrie
AU  - Miceli MC
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Furlong, Pat
AU  - Furlong P
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Landry, John
AU  - Landry J
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Elashoff, Robert
AU  - Elashoff R
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
FAU - Cox, David
AU  - Cox D
AD  - From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of 
      Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), 
      Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle 
      University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), 
      Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, 
      Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA 
      (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), 
      Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and 
      Eli Lilly and Company (D.C.), Indianapolis, IN.
CN  - Tadalafil DMD Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT01865084
GR  - P30 AG028740/AG/NIA NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20170929
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Glucocorticoids)
RN  - 0 (Vasodilator Agents)
RN  - 742SXX0ICT (Tadalafil)
SB  - IM
MH  - Adolescent
MH  - Area Under Curve
MH  - Child
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Follow-Up Studies
MH  - Glucocorticoids/therapeutic use
MH  - Heart Rate/physiology
MH  - Humans
MH  - International Cooperation
MH  - Male
MH  - Muscular Dystrophy, Duchenne/*drug therapy/psychology
MH  - Quality of Life
MH  - Respiratory Function Tests
MH  - Tadalafil/*therapeutic use
MH  - Treatment Outcome
MH  - Vasodilator Agents/*therapeutic use
MH  - Ventricular Function, Left
MH  - Walking/physiology
PMC - PMC5664308
FIR - Abdel-Hamid, Hoda
IR  - Abdel-Hamid H
FIR - Apkon, Susan
IR  - Apkon S
FIR - Barohn, Richard
IR  - Barohn R
FIR - Belousova, Elena
IR  - Belousova E
FIR - Bertini, Enrico
IR  - Bertini E
FIR - Brandsema, John
IR  - Brandsema J
FIR - Bruno, Claudio
IR  - Bruno C
FIR - Burnette, William
IR  - Burnette W
FIR - Butterfield, Russell
IR  - Butterfield R
FIR - Byrne, Barry
IR  - Byrne B
FIR - Campbell, Craig
IR  - Campbell C
FIR - Carlo, Jose
IR  - Carlo J
FIR - Chae, Jong-Hee
IR  - Chae JH
FIR - Chandratre, Saleel
IR  - Chandratre S
FIR - Comi, Giacomo
IR  - Comi G
FIR - Connolly, Anne
IR  - Connolly A
FIR - De Groot, Imelda
IR  - De Groot I
FIR - Deconinck, Nicolas
IR  - Deconinck N
FIR - Dooley, Joseph
IR  - Dooley J
FIR - Dubrovsky, Alberto
IR  - Dubrovsky A
FIR - Durigneux, Julien
IR  - Durigneux J
FIR - Finanger, Erika
IR  - Finanger E
FIR - Finkel, Richard
IR  - Finkel R
FIR - Frank, L Matthew
IR  - Frank LM
FIR - Goemans, Nathalie
IR  - Goemans N
FIR - Harper, Amy
IR  - Harper A
FIR - Hattori, Ayako
IR  - Hattori A
FIR - Herguner, Ozlem
IR  - Herguner O
FIR - Iannaccone, Susan
IR  - Iannaccone S
FIR - Janas, Joanne
IR  - Janas J
FIR - Jong, Yuh-Jyh
IR  - Jong YJ
FIR - Kirschner, JanBerd
IR  - Kirschner J
FIR - Komaki, Hirofumi
IR  - Komaki H
FIR - Kuntz, Nancy
IR  - Kuntz N
FIR - Lee, Wang-Tso
IR  - Lee WT
FIR - Leung, Edward
IR  - Leung E
FIR - Mah, Jean
IR  - Mah J
FIR - Mathews, Katherine
IR  - Mathews K
FIR - McDonald, Craig
IR  - McDonald C
FIR - Mercuri, Eugenio
IR  - Mercuri E
FIR - McMillan, Hugh
IR  - McMillan H
FIR - Mueller-Felber, Wolfgang
IR  - Mueller-Felber W
FIR - Lopez de Munain, Adolfo
IR  - Lopez de Munain A
FIR - Nakamura, Akinori
IR  - Nakamura A
FIR - Niks, Erik
IR  - Niks E
FIR - Ogata, Katsuhisa
IR  - Ogata K
FIR - Pascual, Samuel
IR  - Pascual S
FIR - Pegoraro, Elena
IR  - Pegoraro E
FIR - Pereon, Yann
IR  - Pereon Y
FIR - Renfroe, Ben
IR  - Renfroe B
FIR - Sanka, Ratna Bhavaraju
IR  - Sanka RB
FIR - Schallner, Jens
IR  - Schallner J
FIR - Schara, Ulrike
IR  - Schara U
FIR - Selby, Kathryn
IR  - Selby K
FIR - Sendra, Isabel Illa
IR  - Sendra II
FIR - Servais, Laurent
IR  - Servais L
FIR - Smith, Edward
IR  - Smith E
FIR - Sparks, Susan
IR  - Sparks S
FIR - Topaloglu, Haluk
IR  - Topaloglu H
FIR - Victor, Ron
IR  - Victor R
FIR - Vilchez, Juan Jose
IR  - Vilchez JJ
FIR - Wicklund, Matthew
IR  - Wicklund M
FIR - Wilichoswki, Ekkehard
IR  - Wilichoswki E
FIR - Wong, Brenda
IR  - Wong B
EDAT- 2017/10/04 06:00
MHDA- 2017/11/03 06:00
PMCR- 2017/10/24
CRDT- 2017/10/04 06:00
PHST- 2017/03/21 00:00 [received]
PHST- 2017/07/28 00:00 [accepted]
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2017/11/03 06:00 [medline]
PHST- 2017/10/04 06:00 [entrez]
PHST- 2017/10/24 00:00 [pmc-release]
AID - WNL.0000000000004570 [pii]
AID - NEUROLOGY2017809046 [pii]
AID - 10.1212/WNL.0000000000004570 [doi]
PST - ppublish
SO  - Neurology. 2017 Oct 24;89(17):1811-1820. doi: 10.1212/WNL.0000000000004570. Epub 
      2017 Sep 29.