Effect of γ-Secretase Inhibition on the Progression of Alzheimer's Disease: LY450139 Versus Placebo
Effect of γ-Secretase Inhibition on the Progression of Alzheimer's Disease: LY450139 Versus Placebo
Alzheimer's disease (AD) is a fatal degenerative disease of the brain for which there is no cure. AD causes brain cells to die. AD is thought to be caused by an excess of beta-amyloid (β-amyloid), a sticky protein in the brain that forms amyloid plaques. At autopsy, AD patients are required to have these amyloid plaques in the brain in order to have a definitive diagnosis of AD. Inhibiting the enzyme gamma-secretase (γ-secretase) lowers the production of β-amyloid. Semagacestat (LY450139) is a functional γ-secretase inhibitor and was shown to lower β-amyloid in blood and spinal fluid in humans tested thus far and in blood, spinal fluid, and brain in animals tested thus far. This study used several different tests to measure the effect of semagacestat on both β-amyloid and amyloid plaques for some participants. The build-up of amyloid plaques was measured by a brain scan that takes a picture of amyloid plaques in the brain. Other tests measured the overall function of the brain and brain size in some participants. In this trial, participants who initially received placebo (inactive sugar pill) were, at a certain point in the study, switched over to active drug, semagacestat. In other words, all participants could eventually receive active drug. Participation could last approximately 2 years. Participants taking approved AD medications were permitted to participate in this study and continue taking these medications during the study. All participants who completed this study had the option to continue receiving semagacestat by participating in an open-label study.
Preliminary results from this study (H6L-MC-LFAN [LFAN]) and another similar study (H6L-MC-LFBC [LFBC; NCT00762411]) showed semagacestat did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Study drug was stopped in all studies. Studies LFAN, LFBC, and open-label H6L-MC-LFBF (LFBF; NCT01035138) were amended to continue collecting safety data, including cognitive scores, for at least 7 months. The Clinical Trial Registry (CTR) will reflect results of analyses from the original LFAN protocol in addition to those from the amended LFAN protocol.
Inclusion Criteria:
Exclusion Criteria:
Birmingham, Alabama 35294, United States
Phoenix, Arizona 85006, United States
Sun City, Arizona 85351, United States
Tucson, Arizona 85741, United States
Fresno, California 93720, United States
Lomita, California 90717, United States
Orange, California 92868, United States
Sacramento, California 95817, United States
San Diego, California 92103, United States
Santa Monica, California 90404, United States
Hamden, Connecticut 06518, United States
New Haven, Connecticut 06510, United States
Washington D.C., District of Columbia 20057, United States
Brooksville, Florida 34613, United States
Fort Lauderdale, Florida 33308, United States
Fort Myers, Florida 33912, United States
Miami, Florida 33140, United States
Pompano Beach, Florida 33064, United States
St. Petersburg, Florida 33716, United States
Sunrise, Florida 33351, United States
Tampa, Florida 33613, United States
Tampa Bay, Florida 33613, United States
West Palm Beach, Florida 33407, United States
Chicago, Illinois 60611, United States
Indianapolis, Indiana 46202, United States
Lexington, Kentucky 40503, United States
Shreveport, Louisiana 71101, United States
Baltimore, Maryland 21224, United States
Boston, Massachusetts 02118, United States
Burlington, Massachusetts 01805, United States
West Yarmouth, Massachusetts 02673, United States
Kansas City, Missouri 64111, United States
St Louis, Missouri 63108, United States
Albany, New York 12208, United States
New York, New York 10032, United States
Durham, North Carolina 27705, United States
Raleigh, North Carolina 27607, United States
Winston-Salem, North Carolina 27157, United States
Columbus, Ohio 43210, United States
Toledo, Ohio 43623, United States
Oklahoma City, Oklahoma 73116, United States
Eugene, Oregon 97401, United States
Jenkintown, Pennsylvania 19046, United States
Philadelphia, Pennsylvania 19104, United States
Pittsburgh, Pennsylvania 15213, United States
East Providence, Rhode Island 02914, United States
North Charleston, South Carolina 29406, United States
Salt Lake City, Utah 84108, United States
Bennington, Vermont 05201, United States
Madison, Wisconsin 53705, United States
Buenos Aires, 1425, Argentina
Córdoba, X5004AOA, Argentina
Santa Fe, S3000FWO, Argentina
Hornsby, New South Wales 2077, Australia
Kogarah, New South Wales 2217, Australia
Randwick, Sydney, New South Wales 2013, Australia
Adelaide, South Australia 5000, Australia
Geelong, Victoria 3220, Australia
Heidelberg West, Victoria 3081, Australia
Kew, Victoria 3101, Australia
Nedlands, Western Australia 6009, Australia
Aalst, 9300, Belgium
Antwerp, 2020, Belgium
Bruges, 8000, Belgium
Leuven, 3000, Belgium
Kelowna, British Columbia V1Y3G8, Canada
Penticton, British Columbia V2A5C8, Canada
Québec, Quebec G1R 3X5, Canada
Sherbrooke, Quebec J1H1Z1, Canada
Antofagasta, Chile
Concepción, Chile
Santiago, 6640870, Chile
Santiago, Chile
Valdivia, Chile
Viña del Mar, Chile
Copenhagen, 2100, Denmark
Roskilde, 4000, Denmark
Svendborg, 4000, Denmark
Kuopio, 70210, Finland
Mikkeli, 50100, Finland
Oulu, 90229, Finland
Nice, 06002, France
Rennes, 35000, France
Rouen, 76036, France
Toulouse, 31059, France
Tours, 37044, France
Dresden, 01307, Germany
Göttingen, 37075, Germany
Hanover, 30559, Germany
München, BY 80336, Germany
Regensburg, D-93053, Germany
Siegen, 57072, Germany
Chennai, 600003, India
Hyderabaad, 400082, India
Kolkata, 700054, India
Mangalore, 575002, India
Mumbai, 400050, India
Thiruvananthapuram, 695011, India
Tirupati, 517507, India
Varanasi, 221005, India
Ashkelon, 78306, Israel
Beersheba, 84170, Israel
Haifa, 31096, Israel
Jerusalem, 91240, Israel
Petah Tikva, 49100, Israel
Tel Aviv, 64239, Israel
Tel Litwinsky, 52661, Israel
Milan, 20157, Italy
Pisa, 56126, Italy
Rome, 00153, Italy
Fukui, 910-3113, Japan
Fukuoka, 770-8076, Japan
Kagawa, 761-0793, Japan
Kochi, 780-0842, Japan
Osaka, 590-0018, Japan
Tokushima, 770-8076, Japan
Bialystok, 15402, Poland
Gdynia, 81-361, Poland
Lodz, 92-216, Poland
Lublin, 20-950, Poland
Poznan, 61-606, Poland
Warsaw, 02-507, Poland
Bellair, 4094, South Africa
Bellville, 7530, South Africa
Cape Town, 7925, South Africa
George, 6529, South Africa
Johannesburg, 1709, South Africa
Rosebank, 2132, South Africa
Somerset West, 7130, South Africa
Umhlanga, 4319, South Africa
Albacete, 2006, Spain
Barakaldo, 48903, Spain
Barcelona, 08014, Spain
Madrid, 28034, Spain
Plasencia, 10600, Spain
Malmö, 20502, Sweden
Mölndal, 43185, Sweden
Norrköping, 60172, Sweden
Stockholm, 14186, Sweden
Uddevalla, 45180, Sweden
Bath, Banes BA1 3NG, United Kingdom
Southampton, Hants SO30 3JB, United Kingdom
Liverpool, Merseyside L9 7LJ, United Kingdom
Glasgow, Scotland G20 0XA, United Kingdom
Swindon, Wilts SN1 4JU, United Kingdom
Belfast, BT9 7BL, United Kingdom
Newcastle, NE4 6BE, United Kingdom