TEMPO-3: Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations

Sponsor

Cerevel Therapeutics, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04542499

Collaborator

(none)

368

Enrollment

125

Locations

Arms

28.1

Anticipated Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effect of tavapadon on the change from baseline in total daily hours of "on" time without troublesome dyskinesia in L-Dopa-treated participants with Parkinson's Disease (PD) who are experiencing motor fluctuations.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: Tavapadon Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

368 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon as Adjunctive Therapy for Parkinson's Disease in Levodopa-Treated Adults With Motor Fluctuations (TEMPO-3 Trial)

Actual Study Start Date :

Oct 27, 2020

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tavapadon Participants will receive a tavapadon tablet titrated 5 to 15 milligrams (mg) once daily (QD) orally for 27 weeks.	Drug: Tavapadon Participants will be randomized to receive tavapadon 5 to 15 mg tablet QD orally for 27 weeks. Other Names: PF-06649751 CVL-751
Placebo Comparator: Placebo Participants will receive placebo matching to tavapadon tablet QD orally for 27 weeks.	Drug: Placebo Participants will receive placebo matching to tavapadon QD orally for 27 weeks.

Arm

Intervention/Treatment

Experimental: Tavapadon

Participants will receive a tavapadon tablet titrated 5 to 15 milligrams (mg) once daily (QD) orally for 27 weeks.

Drug: Tavapadon

Participants will be randomized to receive tavapadon 5 to 15 mg tablet QD orally for 27 weeks.

Other Names:

PF-06649751

CVL-751

Placebo Comparator: Placebo

Participants will receive placebo matching to tavapadon tablet QD orally for 27 weeks.

Drug: Placebo

Participants will receive placebo matching to tavapadon QD orally for 27 weeks.

Outcome Measures

Primary Outcome Measures

Change From Baseline in the Total "On" Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) [Up to 27 weeks]
The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total "on" time without troublesome dyskinesia will be assessed and reported at endpoint.

Secondary Outcome Measures

Change From Baseline in Total Daily "Off" Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) [Up to 27 weeks]
The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total daily "Off" time will be assessed and reported at endpoint.
Change From Baseline in the Total "On" Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) [Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27]
The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total "on" time without troublesome dyskinesia will be assessed and reported at different time points.
Change From Baseline in Total Daily "Off" Time Without Troublesome Dyskinesia Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) [Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27]
The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total daily "Off" time will be assessed and reported at different time points.
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score [Up to 27 weeks]
The MDS-UPDRS is a multidimensional scale that assesses the motor and non-motor impacts of PD across 4 parts. Part I, non-motor aspects of experiences of daily living, comprises 13 items, 6 of which are rated by the physician (Part IA) and 7 of which are rated by the participant (Part IB). Part II, motor aspects of experiences of daily living, comprises 13 items that are rated by the participant. Part III, motor examination, comprises 18 items that are assessed by the investigator (resulting in 33 scores by location and lateralization). Part IV, motor complications, comprises 6 item (3 items for dyskinesia and 3 items for fluctuation) and requires the physician to use historical and objective information to assess dyskinesia and motor fluctuations. Each item of all the parts will be rated on a scale from 0 to 4 on which 0 = normal, 1=slight, 2=mild, 3=moderate, and 4=severe. Change from baseline in MDS-UPDRS parts I, II and III Individual score will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Male and female participants aged 40 to 80 years, inclusive, at the time of signing the informed consent form (ICF).
Sexually active men or women of childbearing potential must agree to use acceptable (at minimum) or highly effective birth control, or remain abstinent during the trial and for 4 weeks after the last dose of trial treatment.
Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Participants with a diagnosis of PD that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria, with bradykinesia and motor asymmetry.
Participants with modified Hoehn and Yahr stage 2, 2.5, or 3 in the "on" state.
Participants with a good response to levodopa (L-Dopa) in the judgment of the investigator.
Participants who return a completed self-reported home diary for motor function status (Hauser diary) during the screening period (after diary training and concordance testing has occurred), with recordings for 2 consecutive days (ie, 2 consecutive 24-hour periods) showing at least 2 and half hours of "off" time on each of the 2 days.
Participants who are on a stable dose of L-Dopa for at least 4 weeks prior to screening and are taking a minimum total daily dose of 400 milligram (mg) divided in at least 4 doses per day of standard carbidopa/levodopa or divided in at least 3 doses per day of extended-release carbidopa/levodopa capsules. The carbidopa/levodopa dose and frequency must be maintained for the duration of the trial.
Prior and concurrent use of catechol-O-methyl transferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, amantadine, or anticholinergic drugs is permitted if use was initiated greater than (>) 90 days before signing of the informed consent, the dosage has remained stable for a minimum of 4 weeks before signing of the informed consent, and the dosage will remain stable for the duration of the trial (ie, no change in the COMT, MAO-B inhibitor, or amantadine dose is permitted during the trial).

Key Exclusion Criteria:

Participants with a history or clinical features consistent with essential tremor, atypical or secondary parkinsonian syndrome (including, but not limited to, progressive supranuclear palsy, multiple system atrophy, cortico-basal degeneration, or drug-induced or poststroke parkinsonism).
Participants with a history of nonresponse or insufficient response to L-Dopa at therapeutic dosages.
Participants with a history or current diagnosis of a clinically significant impulse control disorder (Disruptive, Impulse Control, and Conduct Disorder per DSM-5).
Participants with the presence of or history of brain tumor, hospitalization for severe head trauma, epilepsy (as defined by the International League Against Epilepsy), or seizures.
Participants with a history of psychosis or hallucinations within the previous 12 months.
Participants who answer "yes" on the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting the criteria for C-SSRS Item 4 or Item 5 occurred within the last 6 months, OR Participants who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting the criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR Participants who, in the opinion of the investigator, present a serious risk of suicide.
Participants with substance abuse or dependence disorder, including alcohol, benzodiazepines, and opioids, but excluding nicotine, within the past 6 months (180 days).
Participants with dementia or cognitive impairment that, in the judgement of the investigator, would exclude the participant from understanding the ICF or participating in the trial.
Participants with any condition that could possibly affect drug absorption, including bowel resections, bariatric weight loss surgery, or gastrectomy (this does not include gastric banding).
Participants who have a positive result for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) antibodies at screening.
Participants with a history of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias that are not controlled with medical and/or surgical intervention; second- or third-degree atrioventricular block; sick sinus syndrome; severe or unstable angina; or congestive heart failure within the last 12 months. A recent (less than or equal to [<=12] months) history of myocardial infarction with secondary arrhythmias is exclusionary regardless of the therapeutic control.
Participants with a history of neuroleptic malignant syndrome.
Participants who are currently receiving moderate or strong CYP3A4 inducers or CYP3A4 inhibitors (except for topical administration).
Participants with a positive urine drug screen for illicit drugs are excluded and may not be retested or rescreened. Participants with a positive urine drug screen resulting from use of marijuana (any tetrahydrocannabinol-containing product), prescription, or over-the-counter medications or products that, in the investigator's documented opinion, do not signal a clinical condition that would impact the safety of the participant or interpretation of the trial results may continue evaluation for the trial following consultation and approval by the medical monitor
Participants with a Montreal Cognitive Assessment (MoCA) score <26.
Participants with clinically significant orthostatic hypotension (eg, syncope).
Participants with a 12-lead ECG demonstrating a QTcF interval >450 msec.
Participants with moderate or severe renal impairment (creatinine clearance as estimated by Cockcroft-Gault formula <30 mL/min or on dialysis).
Participants with any of the following abnormalities in clinical laboratory tests at the Screening Visit, as assessed by the central laboratory and confirmed by a single repeat measurement, if deemed necessary:
Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) >=3 × Upper Limit Normal (ULN).
Total bilirubin >=1.5 × ULN. Participants with a history of Gilbert's syndrome may be eligible provided they have a value <ULN for direct bilirubin
Participants with other abnormal laboratory test results, vital sign results, or ECG findings unless, in the judgment of the investigator, the findings are not medically significant and would not impact the safety of the participants or the interpretation of the trial results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pheonix, Arizona	Phoenix	Arizona	United States	85004
2	Little Rock, Arkansas	Little Rock	Arkansas	United States	72205
3	Fountain Valley, California	Fountain Valley	California	United States	92708
4	Frenso, California	Fresno	California	United States	93710
5	Long beach, California	Long Beach	California	United States	90806
6	Los Angeles, California	Los Angeles	California	United States	90048
7	Pasadena, California	Pasadena	California	United States	91105
8	Reseda, California	Reseda	California	United States	91335
9	Denver, Colorado	Denver	Colorado	United States	80210
10	Englewood, Colorado	Englewood	Colorado	United States	80113
11	Atlantis, Florida	Atlantis	Florida	United States	33462
12	Boca Raton, Florida	Boca Raton	Florida	United States	33486
13	Coral Springs, Florida	Coral Springs	Florida	United States	33067
14	Adventura, Florida	Florida City	Florida	United States	33180
15	Hallandale Beach, Florida	Hallandale Beach	Florida	United States	33009
16	Maitland, Florida	Maitland	Florida	United States	32751
17	Ocala, Florida	Ocala	Florida	United States	34470
18	Port Charlotte, Florida	Port Charlotte	Florida	United States	33980
19	Tampa, Florida	Tampa	Florida	United States	33615
20	Winter Park, Florida	Winter Park	Florida	United States	32792
21	Augusta, Georgia	Augusta	Georgia	United States	30912
22	Chicago, Illinois	Chicago	Illinois	United States	60612
23	Elk Grove Village, Illinois	Elk Grove Village	Illinois	United States	60007
24	Kansas	Kansas City	Kansas	United States	66160
25	Lexington, Kentucky	Lexington	Kentucky	United States	40536
26	Scarborough, Maine	Scarborough	Maine	United States	04074
27	Farmington Hills, Mitchigan	Farmington Hills	Michigan	United States	48334
28	West Bloomfield, Michigan	West Bloomfield	Michigan	United States	48322
29	Saint Louis, Missouri	Saint Louis	Missouri	United States	63110
30	Las Vegas, Nevada	Las Vegas	Nevada	United States	89106
31	Las Vegas, Nevada,	Las Vegas	Nevada	United States	89118
32	Syracuse, New York	Syracuse	New York	United States	13210
33	Asheville, North Carolina	Asheville	North Carolina	United States	28806
34	Cincinnati, Ohio	Cincinnati	Ohio	United States	45212
35	Cleveland, Ohio	Cleveland	Ohio	United States	44195
36	Columbus, Ohio	Columbus	Ohio	United States	43221
37	Dayton, Ohio	Dayton	Ohio	United States	45459
38	Toledo, Ohio	Toledo	Ohio	United States	43614
39	Memphis, Tennessee	Memphis	Tennessee	United States	38157
40	Georgetown, Texas	Georgetown	Texas	United States	78626
41	Houston, Texas	Houston	Texas	United States	77030
42	Lubbock, Texas	Lubbock	Texas	United States	79410
43	Round Rock, Texas	Round Rock	Texas	United States	78681
44	Burlington, Vermont	Burlington	Vermont	United States	05401
45	Richmond, Virginia	Richmond	Virginia	United States	23229
46	Richmond, Virginia	Richmond	Virginia	United States	23233
47	Virginia Beach, Virginia	Virginia Beach	Virginia	United States	23456
48	Kirkland, Washington	Kirkland	Washington	United States	98034
49	Spokane, Washington	Spokane	Washington	United States	99202
50	Clayton VIC	Clayton	Clayton VIC	Australia	3168
51	Erina, New South Wales	Erina	New South Wales	Australia	2250
52	Kogarah, New South Wales	Kogarah	New South Wales	Australia	2217
53	Woolloongabba, Queensland	Woolloongabba	Queensland	Australia	4102
54	Parkville, Victoria	Parkville	Victoria	Australia	3050
55	Sofia	Sofia		Bulgaria	1113
56	Sofia	Sofia		Bulgaria	1407
57	Sofia	Sofia		Bulgaria	1431
58	Ottawa, Ontario	Ottawa	Ontario	Canada	K1Y4E9
59	Toronto, Ontario	Toronto	Ontario	Canada	M5T 2S8
60	Chocen	Choceň	Chocen	Czechia	565 01
61	Prague	Prague		Czechia	10000
62	Prague 5, Czech Republic	Prague		Czechia	150 00
63	Rychnov nad Kněžnou	Rychnov Nad Kněžnou		Czechia	516 01
64	Creteil,	Créteil	Creteil	France	94010
65	Boulevard Pinel, Bron	Bron		France	69500
66	Nantes CEDEX 1	Nantes		France	44093
67	Nîmes cedex	Nîmes		France	30029
68	Strasbourg	Strasbourg		France	67098
69	Muenster	Münster	Muenster	Germany	48149
70	Berlin	Berlin		Germany	12163
71	Bochum	Bochum		Germany	44791
72	Duesseldorf,	Duesseldorf		Germany	40225
73	Gera	Gera		Germany	07551
74	Haag in Oberbayern	Haag In Oberbayern		Germany	83527
75	Muenchen	Muenchen		Germany	81377
76	Stadtroda	Stadtroda		Germany	07646
77	Gyor,	Győr	Gyor	Hungary	9024
78	Budapest	Budapest		Hungary	1135
79	Pecs	Pécs		Hungary	7623
80	Szeged	Szeged		Hungary	6725
81	Ashkelon	Ashkelon		Israel	7830406
82	Haifa	Haifa		Israel	3109601
83	Jerusalem	Jerusalem		Israel	91120
84	Petah Tiqva	Petah Tiqva		Israel	49100
85	Shoham	Shoham		Israel	6083531
86	Tel Aviv	Tel Aviv		Israel	6100000
87	Ancona	Ancona		Italy	60126
88	Cassino	Cassino		Italy	03043
89	Milano	Milano		Italy	20132
90	Pisa	Pisa		Italy	56126
91	Rome	Rome		Italy	00133
92	Rome	Rome		Italy	00163
93	Rome	Rome		Italy	00179
94	Rozzano Milano	Rozzano		Italy	20089
95	Torino	Torino		Italy	10126
96	Lodz	Łódź	Lodz	Poland	90-640
97	Siemianowice Slaskie	Siemianowice Śląskie	Siemianowice Slaskie	Poland	41-100
98	Katowice	Katowice		Poland	40-097
99	Katowice	Katowice		Poland	40-123
100	Krakow	Krakow		Poland	30-539
101	Krakow	Krakow		Poland	31-505
102	Kraków	Kraków		Poland	30-510
103	Lublin	Lublin		Poland	20-016
104	Warsaw	Warsaw		Poland	01-868
105	Belgrade,	Belgrade		Serbia	11000
106	Belgrade	Belgrade		Serbia	11000
107	Kragujevac	Kragujevac		Serbia	34000
108	Elche	Elche	Alicante	Spain	03203
109	Barcelona	Barcelona		Spain	08035
110	Barcelona	Barcelona		Spain	08041
111	Barcelona	Barcelona		Spain	08190
112	Madrid	Madrid		Spain	28006
113	Pamplona	Pamplona		Spain	31008
114	San Sebastián	San Sebastián		Spain	20009
115	Sevilla	Sevilla		Spain	41013
116	Terrassa	Terrassa		Spain	08222
117	Valencia	Valencia		Spain	46026
118	Zaporiizhzhya	Zaporizhzhya	Zaporiizhzhya	Ukraine	69600
119	Zaporozhya	Zaporozhye	Zaporozhya	Ukraine	69000
120	Zaporozhya	Zaporozhye	Zaporozhya	Ukraine	69068
121	Dnipro	Dnipro		Ukraine	49027
122	Kharkiv	Kharkiv		Ukraine	61058
123	Kiev	Kiev		Ukraine	04114
124	Lviv	Lviv		Ukraine	79010
125	Vinnitsa	Vinnitsa		Ukraine	21050