HealthyPhase 1NCT02431364
Trial of Safety and Tolerability of Oral Verdinexor (KPT-335) in Healthy Adults
A Phase 1 study testing Verdinexor in people with Healthy, run by Karyopharm Therapeutics Inc at 1 site in Australia.
Trial summary
This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and 3 to healthy adult participants. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Verdinexor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteAustralia
- Study dates
- 26 May 2015to 1 Oct 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must be in good health as determined by the investigator, based on the medical history, ECG, physical examination, and safety laboratory tests at screening.
- Participants must be identified as a non-smoker at the screening visit (a non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to the screening visit and who has a ≤ 15 pack year history of lifetime cigarette use). A urine cotinine test will be performed at screening and at the time of clinic check-in prior to study drug treatment.
Who cannot join
- The participant has any surgical or medical condition that potentially may alter the absorption, metabolism, or excretion of the study drug such as gastrectomy, Crohn's disease, or liver disease.
- The participant has a history of clinically significant allergies. Hay fever is allowed unless it is active or has required treatment within the previous 2 months.
- Presence of a chronic condition(s) with clinical or historical evidence of recent exacerbation, or other information to suggest non-control of such condition(s).
- History of alcohol abuse or drug addiction within 12 months of the screening visit.
- Any participant with active cataracts or medical history of cataracts.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential, Dose-Escalating Trial to Evaluate the Safety and Tolerability of Oral Verdinexor (KPT-335) in Healthy Adult Subjects
This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and 3 to healthy adult participants.
Read the detailed description
This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and 3 to healthy adult participants.
Cohorts of 8 participants each (6 active, 2 placebo) will be sequentially administered verdinexor or placebo (one dose on Day 1 and one dose on Day 3) using a dose-escalation scheme. A conservative, sequential, dose-escalation strategy employing decreasing escalation increments will be used.
- Conditions
- Healthy
- Being tested
- Verdinexor, Placebo
- Keywords
- KPT-335, Verdinexor, Karyopharm, First-in-Human, Adult Subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VerdinexorDrug
Also called KPT-335
Participants received verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral
PlaceboOther
Participants received placebo matched to verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received matched placebo tablets to verdinexor tablets orally once daily on Days 1 and 3. Receives: Other: Placebo |
| Verdinexor 5 mg | Experimental | Participants received verdinexor 5 milligrams (mg) (2 tablets of 2.5 mg each) orally once daily on Days 1 and 3. Receives: Drug: Verdinexor |
| Verdinexor 10 mg | Experimental | Participants received verdinexor 10 mg tablet orally once daily on Days 1 and 3. Receives: Drug: Verdinexor |
| Verdinexor 20 mg | Experimental | Participants received verdinexor 20 mg tablet (2 tablets of 10 mg each) orally once daily on Days 1 and 3. Receives: Drug: Verdinexor |
| Verdinexor 40 mg | Experimental | Participants received verdinexor 40 mg tablet (4 tablets of 10 mg each) orally once daily on Days 1 and 3. Receives: Drug: Verdinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. A serious adverse event (SAE) was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, was life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study.
Measured: From start of study drug administration up to Day 33
Secondary outcomes (14)
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) of Verdinexor
AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Area Under the Concentration-time Curve From Time Zero to Extrapolated to Infinity (AUC0-inf) of Verdinexor
AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated). It was calculated as AUC0-t + Ct/kel, where: Ct = the last observed non-zero concentration, kel = elimination rate constant.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Maximum Observed Concentration (Cmax) of Verdinexor
Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Average Plasma Concentration From Time Zero to 24 Hours Post-dose (Cavg0-24h) of Verdinexor
Cavg0-24h was defined as average plasma concentration from time zero to 24 hours post-dose.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24 hours post-dose
Time of First Observation of Maximum Observed Concentration (Tmax) of Verdinexor
Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Elimination Rate Constant (Kel) of Verdinexor
Elimination rate constant was calculated using linear regression on the terminal portion of the log-linear concentration versus time curve.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Elimination Half-life (t1/2) of Verdinexor
t1/2 was defined as elimination half-life, it was calculated as ln(2)/kel.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Apparent Total Body Clearance (Cl/F) of Verdinexor
Apparent total body clearance was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram [kg]).
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Apparent Volume of Distribution (Vd/F) of Verdinexor
Vd/F was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kg).
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Accumulation Factor (AR) of Cmax
An AR was defined as a ratio of mean of Cmax Day 3/ Cmax Day 1 for plasma verdinexor.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Accumulation Factor (AR) of Cavg0-24Hour
An AR was defined as a ratio of mean of Cavg0-24hour Day 3/ Cavg0-24hour Day 1 for plasma verdinexor.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24 hours post-dose
Accumulation Factor (AR) of AUC0-t
An AR factor was defined as a ratio of mean of AUC0-t Day 3/ AUC0-t Day 1 for plasma verdinexor.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Accumulation Factor (AR) of AUC0-inf
Accumulation factor was defined as a ratio of mean of AUC0-inf Day 3/ AUC0-inf Day 1 for plasma verdinexor.
Measured: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Maximum Tolerated Dose (MTD) of Verdinexor
MTD was defined as the dose level tested in the cohort immediately preceding a cohort where one or more dose limiting toxicities (DLTs) were observed. A DLT was defined as any AE or abnormal laboratory value that the Investigator suspected was probably related to verdinexor that was severe in intensity or serious or Indicative of an unacceptable risk to additional participants in the study in the opinion of the Investigator or Sponsor.
Measured: From start of study drug administration up to Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2015 (estimated)
- Study start26 May 2015
- Primary completion1 Oct 2015
- Study completion1 Oct 2015
Why it stopped: Administrative reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karyopharm Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02431364
- Sponsor's protocol ID
- KCP-335-701
- Status last verified
- Jan 2023
- First submitted
- 22 Apr 2015
- Last updated
- 20 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- 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 20 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential, Dose-Escalating Trial to Evaluate the Safety and Tolerability of Oral Verdinexor (KPT-335) in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02431364
- Acronym / sponsor ID
- KCP-335-701
- Conditions
- Healthy
- Keywords
- KPT-335, Verdinexor, Karyopharm, First-in-Human, Adult Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administrative reason
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Karyopharm Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- 26 May 2015 (actual)
- Primary completion
- 1 Oct 2015 (actual)
- Study completion
- 1 Oct 2015 (actual)
- First posted
- 1 May 2015 (estimated)
- Results
- Posted 13 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and 3 to healthy adult participants.
Detailed description
This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and 3 to healthy adult participants.
Cohorts of 8 participants each (6 active, 2 placebo) will be sequentially administered verdinexor or placebo (one dose on Day 1 and one dose on Day 3) using a dose-escalation scheme. A conservative, sequential, dose-escalation strategy employing decreasing escalation increments will be used.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboParticipants received matched placebo tablets to verdinexor tablets orally once daily on Days 1 and 3. |
| Verdinexor 5 mg | Experimental | Drug: VerdinexorParticipants received verdinexor 5 milligrams (mg) (2 tablets of 2.5 mg each) orally once daily on Days 1 and 3. |
| Verdinexor 10 mg | Experimental | Drug: VerdinexorParticipants received verdinexor 10 mg tablet orally once daily on Days 1 and 3. |
| Verdinexor 20 mg | Experimental | Drug: VerdinexorParticipants received verdinexor 20 mg tablet (2 tablets of 10 mg each) orally once daily on Days 1 and 3. |
| Verdinexor 40 mg | Experimental | Drug: VerdinexorParticipants received verdinexor 40 mg tablet (4 tablets of 10 mg each) orally once daily on Days 1 and 3. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Participants must be in good health as determined by the investigator, based on the medical history, ECG, physical examination, and safety laboratory tests at screening.
- Participants must be identified as a non-smoker at the screening visit (a non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to the screening visit and who has a ≤ 15 pack year history of lifetime cigarette use). A urine cotinine test will be performed at screening and at the time of clinic check-in prior to study drug treatment.
Key exclusion criteria (5 listed)
- The participant has any surgical or medical condition that potentially may alter the absorption, metabolism, or excretion of the study drug such as gastrectomy, Crohn's disease, or liver disease.
- The participant has a history of clinically significant allergies. Hay fever is allowed unless it is active or has required treatment within the previous 2 months.
- Presence of a chronic condition(s) with clinical or historical evidence of recent exacerbation, or other information to suggest non-control of such condition(s).
- History of alcohol abuse or drug addiction within 12 months of the screening visit.
- Any participant with active cataracts or medical history of cataracts.
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 |
|---|---|---|
| VerdinexorAlso: KPT-335Participants received verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral | Drug | Verdinexor 10 mg, Verdinexor 20 mg, Verdinexor 40 mg, Verdinexor 5 mg |
| PlaceboParticipants received placebo matched to verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral | Other | Placebo |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From start of study drug administration up to Day 33
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. A serious adverse event (SAE) was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, was life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study.
14 secondary outcomes
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Area Under the Concentration-time Curve From Time Zero to Extrapolated to Infinity (AUC0-inf) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Maximum Observed Concentration (Cmax) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Average Plasma Concentration From Time Zero to 24 Hours Post-dose (Cavg0-24h) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24 hours post-dose
Time of First Observation of Maximum Observed Concentration (Tmax) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Elimination Rate Constant (Kel) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Elimination Half-life (t1/2) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Apparent Total Body Clearance (Cl/F) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Apparent Volume of Distribution (Vd/F) of Verdinexor
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Accumulation Factor (AR) of Cmax
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Accumulation Factor (AR) of Cavg0-24Hour
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24 hours post-dose
Accumulation Factor (AR) of AUC0-t
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Accumulation Factor (AR) of AUC0-inf
Time frame: Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose
Maximum Tolerated Dose (MTD) of Verdinexor
Time frame: From start of study drug administration up to Day 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Verdinexor in people with Healthy, run by Karyopharm Therapeutics Inc at 1 site in Australia.
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 2 inclusion and 5 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: stopped early, as of the sponsor's last update on 20 Jan 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 Australia. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 13 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) (time frame: From start of study drug administration up to Day 33). 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 20 Jan 2023.