Healthy VolunteerPhase 1NCT05489744
Human Mass Balance and Biotransformation Study of [14C]Afuresertib
A Phase 1 study testing [14C]Afuresertib in people with Healthy Volunteer, run by Laekna Limited at 1 site in China.
Trial summary
This study adopts a single-center, single-dose, non-randomized, open-label design with a proposed enrollment of 6-10 healthy male subjects. After a single oral dose of approximately 125 mg/150 µCi [14C]Afuresertib tablets, blood, urine and fecal specimens are collected from each subject at defined time points/periods… Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer
- What is being tested?
- [14C]Afuresertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 6 Aug 2022to 21 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male adults;
- Aged 18-45 years (inclusive);
- BMI: 19-26 kg/m2 (inclusive); body weight ≥ 50 kg;
- Willing to sign the Informed Consent Form (ICF);
- Capable of communicating well with investigators and completing the entire study as required.
Who cannot join
- Abnormal and clinically significant results of physical examination, vital signs, laboratory tests (routine hematology, blood biochemistry, coagulation function, routine urinalysis, fecal occult blood, thyroid function), 12-lead ECG, chest X-ray, and abdominal B-mode ultrasound (liver, gallbladder, pancreas, spleen, kidney);
- Resting QT interval corrected with Fridericia's formula (QTcF) ≥ 450 ms shown on the 12-lead ECG;
- Positive for hepatitis B surface antigen or E antigen, IgG antibody against hepatitis C virus (Anti-HCV IgG), antihuman immunodeficiency virus antigen/antibody (HIV-Ag/Ab) Combo Assay, and treponema pallidum antibody;
- Clinically significant CRP abnormality in SaRS-CoV-2 infection screening or positive for SARS-CoV-2 nucleic acid test;
- Use of any drug that inhibits or induces liver drug-metabolizing enzymes within 30 d before screening (see Appendix 1 for details);
- Use of any prescription drugs, over-the-counter drugs, Chinese herbal medicines or food supplements, such as vitamins and calcium supplements, within 14 d before screening;
Show all 24Show fewer
- History of diabetes mellitus and/or pancreatitis;
- History of any serious disease or condition that may affect the study results in the opinion of the investigators, including but not limited to disorders of the circulatory system, respiratory system, endocrine system, nervous system, digestive system, urinary system, or blood, immune, mentality, or metabolism diseases;
- History of structural heart disease, heart failure, myocardial infarction, angina pectoris, unexplained arrhythmia, torsades de pointes, ventricular tachycardia, atrioventricular block, long QT syndrome (LQTS), symptoms or family history of LQTS (indicated by genetic evidence or sudden death of close relatives due to cardiac causes at a young age);
- Reception of major surgery (included but not limited to any surgery with significant risk of bleeding, prolonged general anesthesia, or significant traumatic injury, or incisional biopsy) within 6 months before the screening period, unhealed surgical wounds;
- Allergic constitution, history of allergy to two or more substances; possibly allergic to the investigational product or its excipients as judged by the investigator;
- Hemorrhoids or perianal disease with regular/ongoing hematochezia, irritable bowel syndrome, inflammatory bowel disease.
- Habitual constipation or diarrhea;
- Alcoholism or regular alcohol consumption within 6 months before screening period, that is, drinking volume > 14 U of alcohol per week (1 U = 360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine); breath alcohol test result > 0 mg/100 mL during the screening period;
- Consumption of more than 5 cigarettes per day or habitual use of nicotine-containing products within 3 months before the screening period, and unable to abstain during the study;
- Abuse of drugs or use of soft drugs (e.g., marijuana) 3 months before the screening period or use of hard drugs (e.g., cocaine, amphetamine, phencyclidine, etc.) 1 year before the screening period; or positive for urine drug test during the screening period;
- Habitual consumption of grapefruit juice or excessive tea, coffee and/or caffeinated beverages, and unable to abstain during the study;
- Long-term exposure to radioactivity, significant radioactive exposure (≥ 2 chest/abdomen CTs, or ≥ 3 other types of X-ray examinations) or participation in radiolabeled drug trials within 1 year prior to the study;
- History of needle or blood sickness, difficulty in collecting blood, or intolerance of venipuncture blood collection;
- Participation in any other clinical trial (including drug and device) within 3 months before the screening period;
- Vaccination within 1 month before the screening period or scheduled vaccination during the study;
- Scheduled for fathering or sperm donation during the study and within 1 year after the study; unwilling to take strict contraceptive measures during the study and within 1 year after the study (see Appendix 3 for details);
- Blood loss or blood donation ≥ 400 mL within 3 months before the screening period, or blood transfusion within 1 month;
- Any factors that render the subjects unsuitable for participating in this study (determined by the investigators).
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
About this study
Official title: In Vivo Absorption, Metabolism, Excretion (AME) Clinical Study of [14C]Afuresertib in Healthy Chinese Male Adults - Human Mass Balance and Biotransformation Study of [14C]Afuresertib
This study adopts a single-center, single-dose, non-randomized, open-label design with a proposed enrollment of 6-10 healthy male subjects. After a single oral dose of approximately 125 mg/150 µCi [14C]Afuresertib tablets, blood, urine and fecal specimens are collected from each subject at defined time points/periods during the trial, and PK parameters, recovery, and excretion routes of [14C]Afuresertib in plasma are calculated by measuring the total radioactivity. The main metabolic and elimination pathways and characteristics of Afuresertib in human, as well as circulating metabolites with close to or higher than 10% of plasma total radioactivity exposure, are also identified by plasma, urine, and fecal radioactive metabolite profiles and major metabolite structure.
Read the detailed description
This study includes two stages:
Stage I: The subjects are subject to the screening examination from D-7 to D-2. Two healthy adult male subjects selected from those who pass the examination are admitted to the clinical research center after qualification against the inclusion and exclusion criteria on D-2, and receive the baseline examination on D-1. After admission, they are trained on medication, urine and feces collection and other procedures to ensure that they can perform related operations in accordance with the protocol and operating manual for biospecimen analysis for mass balance and biotransformation study. Random urine and feces specimens (-24 h to 0 h) are collected on D-1 and the subjects are deprived of food for at least 10 h and water for 1 h before dosing. On the morning of the first day of the study, blood specimens are collected within 1 h before dosing, and the investigational product is taken orally on an empty stomach with 240 mL of warm water. The subjects are deprived of food for 4 h and water for 1 h after dosing. All urine and feces specimens excreted within the specified time intervals of 0-504 h and blood specimens sampled at specified time points before and within 0-504 h after dosing are collected. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results. If the specimen collection time exceeds 504 h, the collection should be extended at an interval of 24 h (urine, feces) or an integer multiple interval of 24 h (plasma) until the criteria for termination of specimen collection specified in the protocol are met. Meanwhile, the safety monitoring is continued until the completion date of the specimen collection.
Stage II: According to the results of the Stage I study, the necessarily for plan adjustment (dosing regimen, biospecimen collection, etc.) is evaluated, and another 4-8 subjects will be selected if necessary.
- Conditions
- Healthy Volunteer
- Being tested
- [14C]Afuresertib
- Keywords
- Mass balance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[14C]AfuresertibDrug
Also called [14C]LAE002
Suspension containing approximately 125 mg of Afuresertib (containing 150 µCi of [14C]Afuresertib) is administered orally on an empty stomach, with approximately 240 mL of water for suspending and drug taking.
| Study group | Role | What they receive |
|---|---|---|
| 125 mg [14C]Afuresertib | Experimental | 125 mg/150 µCi [14C]Afuresertib (125 mg of Afuresertib containing 150 µCi of [14C]Afuresertib) Receives: Drug: [14C]Afuresertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantitatively analyze total radioactivity in the excreta.
Quantitatively analyze total radioactivity in the excreta of healthy male subjects after oral administration of [14C]Afuresertib to calculate the excretion of radioactivity in human body and confirm the main excretion route of the drug.
Measured: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
Pharmacokinetics (PK) analysis of radioactivity in plasma will be measured.
The total radioactivity in collected plasma and urine specimens is determined by a liquid scintillation counter.
The collected whole blood and feces homogenate specimens are combusted by an oxidation combustor, and the total radioactivity is measured and calculated by a liquid scintillation counter.
Measured: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
Identify the main biotransformation pathways and the major metabolites by HPLC-MS/MS.
Each mixed specimen is processed by appropriate methods, and followed by the combination of HPLC and on-line or off-line isotope detector to obtain radioisotope metabolite profile.
The major metabolites in plasma, urine and feces specimens are identified by HPLC-MS/MS.
Cumulative recovery of total radioactivity in urine and/or feces will be measured by HPLC-MS/MS.
Measured: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
Quantitatively analyze the concentration of Afuresertib and its metabolites by the validated HPLC-MS/MS.
Quantitatively analyze the concentration of Afuresertib and its metabolites (if applicable) in plasma using a validated HPLC-MS/MS method to obtain the PK parameters in plasma.
Percentage of each metabolite in urine and feces to the dose (%dose) or percentage of circulating metabolites in plasma to total exposure AUC (% AUC).
Measured: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
Secondary outcomes (1)
Safety and tolerability of Afuresertib as measured by adverse events (AEs) .
The cases of AEs, number of subjects and incidence are calculated, and listed by system organ class (SOC) and preferred term (PT). A detailed list of various AEs is also made. The severity of AEs and SAEs and the relationship with the investigational product are summarized separately.
Measured: During the screening period, at Day-2, Day-1, before dosing (within 1 hour before dosing) and at 4, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, and 504 hours after dosing.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2022
- Study start6 Aug 2022
- Primary completion21 Oct 2022
- Study completion21 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laekna Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Liyan Miao, Principal investigator, The First Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05489744
- Sponsor's protocol ID
- LAE002CN1001
- Status last verified
- May 2023
- First submitted
- 12 Jul 2022
- Last updated
- 15 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vivo Absorption, Metabolism, Excretion (AME) Clinical Study of [14C]Afuresertib in Healthy Chinese Male Adults - Human Mass Balance and Biotransformation Study of [14C]Afuresertib
- ClinicalTrials.gov ID
- NCT05489744
- Acronym / sponsor ID
- LAE002CN1001
- Conditions
- Healthy Volunteer
- Keywords
- Mass balance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Laekna LimitedIndustry (pharma, biotech, devices)
- Study start
- 6 Aug 2022 (actual)
- Primary completion
- 21 Oct 2022 (actual)
- Study completion
- 21 Oct 2022 (actual)
- First posted
- 5 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study adopts a single-center, single-dose, non-randomized, open-label design with a proposed enrollment of 6-10 healthy male subjects. After a single oral dose of approximately 125 mg/150 µCi [14C]Afuresertib tablets, blood, urine and fecal specimens are collected from each subject at defined time points/periods during the trial, and PK parameters, recovery, and excretion routes of [14C]Afuresertib in plasma are calculated by measuring the total radioactivity. The main metabolic and elimination pathways and characteristics of Afuresertib in human, as well as circulating metabolites with close to or higher than 10% of plasma total radioactivity exposure, are also identified by plasma, urine, and fecal radioactive metabolite profiles and major metabolite structure.
Detailed description
This study includes two stages:
Stage I: The subjects are subject to the screening examination from D-7 to D-2. Two healthy adult male subjects selected from those who pass the examination are admitted to the clinical research center after qualification against the inclusion and exclusion criteria on D-2, and receive the baseline examination on D-1. After admission, they are trained on medication, urine and feces collection and other procedures to ensure that they can perform related operations in accordance with the protocol and operating manual for biospecimen analysis for mass balance and biotransformation study. Random urine and feces specimens (-24 h to 0 h) are collected on D-1 and the subjects are deprived of food for at least 10 h and water for 1 h before dosing. On the morning of the first day of the study, blood specimens are collected within 1 h before dosing, and the investigational product is taken orally on an empty stomach with 240 mL of warm water. The subjects are deprived of food for 4 h and water for 1 h after dosing. All urine and feces specimens excreted within the specified time intervals of 0-504 h and blood specimens sampled at specified time points before and within 0-504 h after dosing are collected. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results. If the specimen collection time exceeds 504 h, the collection should be extended at an interval of 24 h (urine, feces) or an integer multiple interval of 24 h (plasma) until the criteria for termination of specimen collection specified in the protocol are met. Meanwhile, the safety monitoring is continued until the completion date of the specimen collection.
Stage II: According to the results of the Stage I study, the necessarily for plan adjustment (dosing regimen, biospecimen collection, etc.) is evaluated, and another 4-8 subjects will be selected if necessary.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 125 mg [14C]Afuresertib | Experimental | Drug: [14C]Afuresertib125 mg/150 µCi [14C]Afuresertib (125 mg of Afuresertib containing 150 µCi of [14C]Afuresertib) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy male adults;
- Aged 18-45 years (inclusive);
- BMI: 19-26 kg/m2 (inclusive); body weight ≥ 50 kg;
- Willing to sign the Informed Consent Form (ICF);
- Capable of communicating well with investigators and completing the entire study as required.
Key exclusion criteria (24 listed)
- Abnormal and clinically significant results of physical examination, vital signs, laboratory tests (routine hematology, blood biochemistry, coagulation function, routine urinalysis, fecal occult blood, thyroid function), 12-lead ECG, chest X-ray, and abdominal B-mode ultrasound (liver, gallbladder, pancreas, spleen, kidney);
- Resting QT interval corrected with Fridericia's formula (QTcF) ≥ 450 ms shown on the 12-lead ECG;
- Positive for hepatitis B surface antigen or E antigen, IgG antibody against hepatitis C virus (Anti-HCV IgG), antihuman immunodeficiency virus antigen/antibody (HIV-Ag/Ab) Combo Assay, and treponema pallidum antibody;
- Clinically significant CRP abnormality in SaRS-CoV-2 infection screening or positive for SARS-CoV-2 nucleic acid test;
- Use of any drug that inhibits or induces liver drug-metabolizing enzymes within 30 d before screening (see Appendix 1 for details);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [14C]AfuresertibAlso: [14C]LAE002Suspension containing approximately 125 mg of Afuresertib (containing 150 µCi of [14C]Afuresertib) is administered orally on an empty stomach, with approximately 240 mL of water for suspending and drug taking. | Drug | 125 mg [14C]Afuresertib |
Primary outcome
Quantitatively analyze total radioactivity in the excreta.
Time frame: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
Quantitatively analyze total radioactivity in the excreta of healthy male subjects after oral administration of [14C]Afuresertib to calculate the excretion of radioactivity in human body and confirm the main excretion route of the drug.
Pharmacokinetics (PK) analysis of radioactivity in plasma will be measured.
Time frame: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
The total radioactivity in collected plasma and urine specimens is determined by a liquid scintillation counter. The collected whole blood and feces homogenate specimens are combusted by an oxidation combustor, and the total radioactivity is measured and calculated by a liquid scintillation counter.
Identify the main biotransformation pathways and the major metabolites by HPLC-MS/MS.
Time frame: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
Each mixed specimen is processed by appropriate methods, and followed by the combination of HPLC and on-line or off-line isotope detector to obtain radioisotope metabolite profile. The major metabolites in plasma, urine and feces specimens are identified by HPLC-MS/MS. Cumulative recovery of total radioactivity in urine and/or feces will be measured by HPLC-MS/MS.
Quantitatively analyze the concentration of Afuresertib and its metabolites by the validated HPLC-MS/MS.
Time frame: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.
Quantitatively analyze the concentration of Afuresertib and its metabolites (if applicable) in plasma using a validated HPLC-MS/MS method to obtain the PK parameters in plasma. Percentage of each metabolite in urine and feces to the dose (%dose) or percentage of circulating metabolites in plasma to total exposure AUC (% AUC).
1 secondary outcome
Safety and tolerability of Afuresertib as measured by adverse events (AEs) .
Time frame: During the screening period, at Day-2, Day-1, before dosing (within 1 hour before dosing) and at 4, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, and 504 hours after dosing.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
Related trials for Healthy Volunteer
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liyan Miao principal investigator
The First Affiliated Hospital of Soochow University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [14C]Afuresertib in people with Healthy Volunteer, run by Laekna Limited at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantitatively analyze total radioactivity in the excreta. (time frame: 0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023.