A Study of TAK-510 in Healthy Adults

Healthy Participants Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-510 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04731922
• Other study ID #: TAK-510-1001
• Secondary ID: U1111-1261-6974
• Status: Completed
• Phase: Phase 1
• Start date: February 3, 2021
• Est. completion date: July 24, 2022

Study information

• Verified date: July 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study of TAK-510 for people with symptoms of feeling sick (nausea) or being sick (vomiting).

The main aims of the study are to check if healthy adults have side effects from TAK-510 and to check how much TAK-510 they can receive without getting side effects from it.

The study will be in 3 parts. Participants will take part in only 1 of the 3 parts of the study.

At the first visit, the study doctor will check if each person can take part. For those who can take part, they will be placed in 1 of many small groups. The 1st groups will join Part 1 of the study, the 2nd groups will join Part 2 and the 3rd groups will join Part 3. They will receive an injection under the skin of either TAK-510 or placebo. In this study, a placebo will look like the TAK-510 injection but will not have any medicine in it.

In Part 1, the 1st group of participants will receive 1 injection of either TAK-510 or placebo. Different participants within this group will receive lower to higher doses of TAK-510. The participants in this group will stay in the clinic for 4 days after their injection for some tests and check for any side effects from their treatment.

In Part 2, the 2nd group of participants will receive an injection of either TAK-510 or placebo, once a day for 5 days. Different participants within this group will receive lower to higher doses of TAK-510. The participants in this group will stay in the clinic for 9 days after their 1st injection for some tests and check for any side effects from their treatment.

In Part 3, the 3rd group of participants will visit the clinic 2 times. At the 1st visit, they will receive an injection either of TAK-510 or placebo, once a day for 7 days. Each participant in this group will receive lower to higher doses of TAK-510. They will stay in the clinic for 8 days after their 1st injection for some tests and check for any side effects from their treatment.

At the 2nd clinic visit, each participant will receive 1 single injection of TAK-510 or placebo. This will happen 7 days after their last injection from the previous clinic visit. They will receive the same dose as their previous dose. They will stay in the clinic for 3 days for some tests and check for any side effects from their treatment.

After treatment, all participants in the study will return to the clinic for a weekly check-up visit for up to 3 weeks.

Description:

The drug being tested in this study is called TAK-510. The study will look at the safety, tolerability, and PK of TAK-510 in healthy participants.

The study will enroll up to approximately 224 healthy participants. Participants in each cohort will be randomized to receive treatment with TAK-510 or matching placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). The study consists of 3 parts and up to 28 cohorts as mentioned below.

• TAK-510, Part 1: Single rising dose (SRD) design to assess the safety, immunogenicity, tolerability, and PK of TAK-510

• TAK-510, Part 2: Multiple rising dose (MRD) design to assess the safety, immunogenicity, tolerability, and PK of TAK-510

• TAK-510, Part 3: Dose titration and redosing design to assess the safety, immunogenicity, tolerability, and PK of TAK-510

This multi-center trial will be conducted in the United States. The overall duration of the study is approximately 57 days. Participants will be followed up for 7 days after the last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: July 24, 2022
• Est. primary completion date: July 24, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Continuous nonsmoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to dosing and throughout the study.

• Body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 30.0 kilogram per square meter (kg/m^2) at the screening visit.

Exclusion Criteria:

• Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody/antigen, at the screening visit.

• Had major surgery or donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the screening visit.

• Unable to refrain from or anticipates using all medications including herbal medicines beginning approximately 7 days before administration of the first dose of study drug, throughout the study until 2 days after discharge.

• Unable to refrain from or anticipates using marijuana or cannabis-containing products beginning approximately 7 days before administration of the first dose of study drug, throughout the study until after the last PK dose.

• Has had a previous major psychotic disorder.

• Has an average semirecumbent blood pressure (BP) less than 90/60 millimeter of mercury (mmHg) or greater than 140/90 mmHg from screening to predose, inclusive. Any assessments on Day -1, where 2 consecutive time point values do not meet this criterion must be discussed with the medical monitor for approval.

• Has orthostatic hypotension defined as a decrease in systolic BP >=20 mmHg or a decrease in diastolic BP >=10 mmHg at approximately 3 minutes of standing when compared with BP from the semirecumbent position, at screening to predose assessments, inclusive. In asymptomatic participants, any assessments after screening that do not meet this criterion may be repeated after the participant has remained in the semirecumbent or supine position for 15 minutes. If the repeat assessment is exclusionary based on the above criterion, the participant will not be eligible. If the repeat assessment is not exclusionary, the participant will be eligible.

• Has postural orthostatic tachycardia, defined as an increase of greater than (>) 30 beats per minute (bpm) or heart rate (HR) >120 bpm at approximately 3 minutes, of standing, at screening to predose assessments, inclusive. Any assessments after screening that do not meet this criterion may be repeated with the participant remaining standing for up to a total of 5 minutes, provided that the participant remains asymptomatic. If the repeat assessment occurring within 5 minutes is exclusionary based on the above criterion, the participant will not be eligible. A confirmed orthostatic increase of >30 bpm, but less than (<) 40 bpm, on 1 or more Day -1 assessments may not be considered exclusionary if not considered clinically significant by the investigator and the medical monitor. Such assessments must be discussed with the medical monitor prior to determination that the participant is eligible to proceed.

• Has a known or suspected current coronavirus disease 2019 (COVID-19) infection or is at risk of COVID-19 infection as assessed by the investigator.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• TAK-510
TAK-510 solution.
• TAK-510 Placebo
TAK-510 placebo-matching solution.

Locations

Country	Name	City	State
United States	PPD Development, LP	Austin	Texas
United States	PPD Development, LP	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Parts 1 and 2, Cmax: Maximum Observed Plasma Concentration for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 96 hours) post-dose; Part 2, Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose
Other	Part 1, AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Parts 1 and 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 96 hours) post-dose; Part 2, Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose
Other	Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 1, CL/F: Apparent Clearance After Extravascular Administration for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 1, Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, AUCt: Area Under the Plasma Concentration-time Curve Over a Dosing Interval for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose
Other	Part 2, AUCtss: Area Under the Plasma Concentration-time Curve Over a Dosing Interval at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, Cmaxss: Maximum Observed Plasma Concentration at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, Tmaxss: Time to Reach the Maximum Observed Plasma Concentration at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, T1/2z: Terminal Disposition Phase Half-life at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, CL/F: Apparent Clearance After Extravascular Administration at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, Ctrough: Observed Plasma Concentration at the End of a Dosing Interval at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, Rac (AUC): Accumulation Ratio Based on AUCt at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Part 2, Rac (Cmax): Accumulation Ratio Based on Cmax at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 96 hours) post-dose
Other	Parts 1 and 2, Aet: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Parts 1 and 2, Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose
Other	Parts 1 and 2, Aet1-t2: Amount of Drug Excreted in Urine From Time 1 to Time 2 for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose; Part 2, Days 1 and 5: pre-dose and at multiple time points (up to 24 hours) post-dose
Other	Part 2, Aet: Amount of Drug Excreted in Urine During a Dosing Interval (Tau) at Steady State for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 2, Day 5: pre-dose and at multiple time points (up to 24 hours) post-dose
Other	Parts 1 and 2, fe,t: Fraction of Administered Dose of Drug Excreted From Urine From Time 0 to Time t for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose; Part 2, Days 1 and 5: pre-dose and at multiple time points (up to 24 hours) post-dose
Other	Parts 1 and 2, CLR: Renal Clearance for TAK-510	Due to confidentiality reasons and chances of exposing the doses for TAK-510, the data for this pharmacokinetic outcome measure was not reported.	Part 1, Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose; Part 2, Days 1 and 5: pre-dose and at multiple time points (up to 24 hours) post-dose
Primary	Parts 1 and 2: Number of Participants Who Met the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose	Vital signs included systolic and diastolic blood pressure, body temperature, pulse rate (PR), respiratory rate, orthostatic blood pressure and pulse rate assessments. The markedly abnormal value (MAV) criteria for vital signs were systolic blood pressure (SBP) less than (<) 85 millimeter of mercury (mmHg), greater than (>) 180 mmHg; diastolic blood pressure (DBP) <50 mmHg, >110 mmHg; body temperature <35.6 degree Celsius, >37.7 degree Celsius; PR <50 beats per minute (bpm), >120 bpm; respiratory rate <12 breaths per minute (breaths/minute), >16 breaths/minute; orthostatic hypotension decrease in SBP greater than or equal to (>=) 20 mmHg or a decrease in DBP >=10 mmHg on standing; orthostatic tachycardia defined as an increase of >30 bpm or heart rate (HR) >120 bpm on standing. Number of participants who met the MAV criteria for vital signs at least once post dose were reported.	Parts 1 and 2: From the first dose of study drug up to Day 29
Primary	Parts 1 and 2: Number of Participants Who Met the Markedly Abnormal Criteria for Electrocardiogram (ECG) Parameters at Least Once Post Dose	ECG included HR, PR, QT interval with Fridericia correction (QTcF) interval and QRS duration. The MAV criteria for 12-lead ECG parameters included heart rate <50 bpm, >120 bpm; PR interval less than or equal to (<=)80 milliseconds (msec), >=200 msec; QTcF interval >=500 msec; QRS duration <=80 msec, >=120 msec. Number of participants who met the MAV criteria for ECG parameters at least once post dose were reported.	Parts 1 and 2: From the first dose of study drug up to Day 29
Primary	Parts 1 and 2: Number of Participants Who Met the Markedly Abnormal Criteria for Laboratory Value at Least Once Post Dose	Clinical laboratory parameters included tests for chemistry and hematology. The MAV criteria for laboratory value included hemoglobin <0.8*LLN,>1.2*ULN; hematocrit <0.8*LLN,>1.2*ULN;RBC count <0.8*LLN, >1.2*ULN;WBC count <0.5*LLN, >1.5*ULN; platelet count <75*10^9 per liter, >600*10^9 per liter; ALT >3*ULN; AST >3*ULN,GGT >3*ULN, normal baseline; >2*baseline,abnormal baseline; ALP>3*ULN, normal baseline; >2*baseline, abnormal baseline; total bilirubin >1.5*ULN, normal baseline; >1.5* baseline, abnormal baseline; albumin <25g/L; total protein <0.8* LLN, >1.2*ULN; creatinine >177 micromole per liter; blood urea nitrogen >10.7 mmol/L; sodium <130 mmol/L, >150mmol/L; potassium <3.0mmol/L, >5.5 mmol/L; glucose <3mmol/L, >10mmol/L; chloride <75mmol/L, >126mmol/L; calcium corrected serum calcium of	Parts 1 and 2: From the first dose of study drug up to Day 29
Primary	Parts 1 and 2: Number of Participants Reporting One or More Treatment-emergent Adverse Event (TEAE)	A TEAE was defined as an adverse event (AE) that started or worsened after first dose of the study treatment and within 30 days of last dose of study treatment. An AE was defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it did not necessarily had to have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it was considered related to the drug.	From the first dose of study drug until 30 days after last dose in Parts 1 and 2 (SRD Cohorts: up to Day 31, MRD Cohorts: up to Day 35)
Secondary	Part 3, Number of Participants Who Met the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens	Vital signs included systolic and diastolic blood pressure, body temperature, PR, respiratory rate, orthostatic blood pressure and pulse rate assessments. The MAV criteria for vital signs were systolic SBP < 85 mmHg, >180 mmHg; DBP <50 mmHg, >110 mmHg; body temperature <35.6 degree Celsius, >37.7 degree Celsius; PR <50 bpm, >120 bpm; respiratory rate <12 breaths/minute, >16 breaths/minute; orthostatic hypotension decrease in SBP >=20 mmHg or a decrease in DBP >=10 mmHg on standing; orthostatic tachycardia defined as an increase of >30 bpm or HR >120 bpm on standing. Sponsor decided not to conduct Part 3 after comprehensive review of available data. No participants were enrolled in Part 3 of the study. Hence, no data collection and assessment were done in Part 3.	Part 3: From the first dose of study drug up to Day 29
Secondary	Part 3, Number of Participants Who Met the Markedly Abnormal Criteria for ECG Parameters at Least Once Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens	ECG included HR, PR, QT QTcF interval and QRS duration. The MAV criteria for 12-lead ECG parameters included heart rate <50 bpm, >120 bpm; PR interval <=80 msec, >=200 msec; QTcF interval >=500 msec or >=30 msec change from baseline and >=450 msec; QRS duration <=80 msec, >=120 msec. Sponsor decided not to conduct Part 3 after comprehensive review of available data. No participants were enrolled in Part 3 of the study. Hence, no data collection and assessment were done in Part 3.	Part 3: From the first dose of study drug up to Day 29
Secondary	Part 3, Number of Participants Who Met the Markedly Abnormal Criteria for Laboratory Value at Least Once Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens	MAV criteria: hemoglobin <0.8*LLN,>1.2*ULN; hematocrit <0.8*LLN,>1.2*ULN;RBC count <0.8*LLN, >1.2*ULN;WBC count <0.5*LLN, >1.5*ULN; platelet count <75*10^9 per liter, >600*10^9 per liter; ALT >3*ULN; AST >3*ULN,GGT >3*ULN, normal baseline; >2*baseline,abnormal baseline; ALP>3*ULN, normal baseline; >2*baseline, abnormal baseline; total bilirubin >1.5*ULN, normal baseline; >1.5* baseline, abnormal baseline; albumin <25g/L; total protein <0.8* LLN, >1.2*ULN; creatinine >177 micromole per liter; blood urea nitrogen >10.7 mmol/L; sodium <130 mmol/L, >150mmol/L; potassium <3.0mmol/L, >5.5 mmol/L; glucose <3mmol/L, >10mmol/L; chloride <75mmol/L, >126mmol/L; calcium corrected serum calcium of	Part 3: From the first dose of study drug up to Day 29
Secondary	Part 3, Number of Participants Reporting One or More TEAE Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens	A TEAE was defined as an AE that started or worsened after first dose of the study treatment and within 30 days of last dose of study treatment. An AE was defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it did not necessarily had to have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it was considered related to the drug. Sponsor decided not to conduct Part 3 after comprehensive review of available data. No participants were enrolled in Part 3 of the study. Hence, no data collection and assessment were done in Part 3.	Part 3: From the first dose of study drug until 30 days after last dose (up to Day 37)
Secondary	Parts 1 and 2: Number of Participants Based on Antidrug Antibody (ADA) Status (Positive and Negative) in Serum	A 3-tiered ADA testing strategy was used in this study. A sample was initially screened for ADA by the ADA screening assay. Any positive sample in the screening assay was considered a potential positive, which was confirmed for true positivity by the confirmatory assay. If a sample was confirmed as an ADA true positive, ADA titer was assessed. ADA positive was defined as participants who had confirmed positive ADA status in at least 1 postbaseline assessments. ADA negative was defined as participants who did not have a confirmed negative ADA status in any post-baseline assessment.	Parts 1 and 2: From the first dose of study drug up to Day 29
Secondary	Part 3: Number of Participants Based on ADA Status (Positive and Negative) in Serum	A 3-tiered ADA testing strategy was used in this study. A sample was initially screened for ADA by the ADA screening assay. Any positive sample in the screening assay was considered a potential positive, which was confirmed for true positivity by the confirmatory assay. If a sample was confirmed as an ADA true positive, ADA titer was assessed. ADA positive was defined as participants who had confirmed positive ADA status in at least 1 postbaseline assessments. ADA negative was defined as participants who did not have a confirmed negative ADA status in any post-baseline assessment. Sponsor decided not to conduct Part 3 after comprehensive review of available data. No participants were enrolled in Part 3 of the study. Hence, no data collection and assessment were done in Part 3.	Part 3: From the first dose of study drug up to Day 29
Secondary	Parts 1 and 2: Number of ADA Positive Participants Based on Low or High ADA Titer	The high ADA titer was defined as participant who has at least 1 post-baseline ADA titer >16 and low ADA titer was defined as participant whose postbaseline ADA titers are all <=16. The low or high ADA titer was assessed in ADA positive participants only.	Parts 1 and 2: From the first dose of study drug up to Day 29
Secondary	Part 3: Number of ADA Positive Participants Based on Low or High ADA Titer	The high ADA titer was defined as participant who has at least 1 post-baseline ADA titer >16 and low ADA titer was defined as participant whose postbaseline ADA titers are all <=16. Sponsor decided not to conduct Part 3 after comprehensive review of available data. No participants were enrolled in Part 3 of the study. Hence, no data collection and assessment were done in Part 3.	Part 3: From the first dose of study drug up to Day 29