The purpose of this study is to characterize the multiple-dose safety and tolerability profile of TAK-935 in adult participants with developmental and/or epileptic encephalopathies.
The drug being tested in this study is called TAK-935. TAK-935 is being tested to treat people who have developmental and/or epileptic encephalopathies. This study will look at safety, tolerability and pharmacokinetics of people who take TAK-935. Study drug will be administered in a double-blind manner in Part 1 and in an open-label manner in Part 2. The study will enroll approximately 20 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in Part 1-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * TAK-935 * Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient Participants will receive placebo or 100 milligram (mg) TAK-935 tablets, orally or through stable G-tube/PEG tube, BID, in Part 1 (Day 1) and dose will be increased to 200 mg (Day 11) BID and to 300 mg (Day 21) BID in dose titration period. All participants who complete the Double-Blind Treatment Period in Part 1 will have the option to continue directly into the Open-Label Treatment Period in Part 2 where they will receive TAK-935 as two 100 mg tablets (total dose is 200 mg TAK-935) orally or through G-tube/PEG tube, BID and dose will be increased to three 100 mg tablets (total dose is 300 mg TAK-935), orally, BID (Day 41). This dose level will be maintained until the final visit (Day 85) for the dose de-escalation phase. This multi-center trial will be conducted in North America. The overall time to participate in this study is 121 days excluding screening period of 30-41 days. Participants will make multiple visits to the clinic, and a follow-up phone call will be conducted on Day 91 and at the end of the 30-day follow-up period (Day 121), participants will return to the clinic for a follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
18
Xenoscience
Phoenix, Arizona, United States
Medsol Clinical Research Center
Port Charlotte, Florida, United States
University of South Florida
Tampa, Florida, United States
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE), as Reported by the Participants or Participant's Caregivers or Observed by the Investigator, After TAK-935 Treatment
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug
Time frame: From first dose up to 30 days post last dose (approximately up to 120 days)
Drug Clearance (CL) and Intercompartmental Clearance (Q) for TAK-935 Calculated Using the Observed Value of the Last Quantifiable Concentration
Time frame: Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose
Apparent Volume of Distribution (Vz/F) of Central Compartment (Vc) and Peripheral Compartment (Vp) for TAK-935 Calculated Using the Observed Value of the Last Quantifiable Concentration
Time frame: Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose
Absorption Rate Constant (Ka) for TAK-935
Time frame: Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose
Cmax,ss: Maximum Observed Plasma Concentration for TAK-935 at Steady State
Time frame: Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose
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Center for Integrative Rare Disease Research
Atlanta, Georgia, United States
Bluegrass Epilepsy Research
Lexington, Kentucky, United States
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, United States
The Comprehensive Epilepsy Care Center for Children and Adults
St Louis, Missouri, United States
Northeast Regional Epilepsy Group
Hackensack, New Jersey, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
...and 1 more locations
AUC0-tau,ss: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for TAK-935 at Steady State
Time frame: Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose
Cav,ss: Average Plasma Concentration During a Dosing Interval at Steady State for TAK-935
Time frame: Day 1 pre-dose and at multiple timepoints (up to 5 hours) post-dose; Days 11 and 21 pre-dose and 1-hour post-dose; Days 31, 41, and 85 pre-dose
Ctrough,ss: Plasma Concentration Immediately Prior to Dosing for TAK-935 at Steady State
Time frame: Days 1, 11, 21; Days 31, 41 and 85 pre-dose
Percentage of Participants With at Least 1 Markedly Abnormal Value for Clinical Laboratory Evaluations After TAK-935
Clinical Laboratory parameters: hematology, serum chemistry and urinalysis. Participants with at least 1 markedly abnormal values during treatment period were reported: Erythrocytes: \<0.8xLLN-\>1.5xULN, Hematocrit: \<0.8x LLN \>1.2xULN,Hemoglobin: \<0.8xLLN-\>1.2xULN Leukocytes: \<0.5xLLN, Platelets (10\^9/L): \<75x10\^9/L-\>600x10\^9/L, Prothrombin Ratio: \>1.5xULN, Alanine Aminotransferase: \>3xULN, Albumin:\<25 g/L, Alkaline Phosphatase: \>3xULN,Alpha-1 Acid Glycoprotein: \<47 mg/DL-\>125 mg/DL, Aspartate Aminotransferase:\>3xULN, Bicarbonate:\<8.0 mmol/L, Calcium:\<1.75 mmol/L-\>2.88 mmol/L, Chloride:\<75 mmol/L-\>126 mmol/L, Cholesterol: \>7.72,Creatine Kinase:\>5xULN, Creatinine:\>177 umol/L, Gamma Glutamyl Transferase: \>3xULN, Glucose:\<2.8 mmol/L- \>19.4 mmol/L,HDL Cholesterol: \<1.04 mmol/L-\>1.55 mmol/L, LDL Cholesterol: \<1.30 mmol/L-\>4.14 mmol/L, Potassium:\<3.0 mmol/L-\>6.0 mEq/L, Protein:\<0.8xLLN-\>1.2 x ULN, Sodium: \<130 mmol/L-\>150 mmol/L, Triglycerides: \>2.5xULN, Urea Nitrogen: \>10.7 mmol/L.
Time frame: From first dose up to last dose (up to Day 85)
Percentage of Participants With at Least 1 Markedly Abnormal Value for Vital Signs After TAK-935
Vital signs included heart rate, blood pressure and body temperature. markedly abnormal values during treatment period were categorized as: heart rate 1,3 and 5 min standing (beats/min) \<50-\>120, systolic blood pressure 1,3 and 5 min standing (mmHg) \<85-\>180, diastolic blood pressure 1,3 and 5 min standing (mmHg) \<50-\>110 and body temperature (degree centigrade) \<35.6- \>37.7. Only categories with values have been reported.
Time frame: From first dose up to 30 days post last dose (approximately up 120 days)
Percentage of Participants With at Least 1 Markedly Abnormal Value for Electrocardiogram (ECG) Parameters After TAK-935
A 12-lead ECG was performed. Markedly abnormal values during treatment period were categorized as: ECG ventricular rate \<50-\>120, PR Interval, (msec) \<=80-\>=200, QRS Duration, (msec) \<=80-\>=180, QT Interval, (msec) \<=50-\>=460, QTcF Interval, (msec) \<=50-\>=500 OR \>=30 change from baseline and \>=450 milliseconds, RR interval \<600-\>=1440.
Time frame: From first dose up to last dose (up to Day 85)