Hepatitis BPhase 1NCT04309526
Safety, Tolerability and Pharmacokinetics of NCO-48 Fumarate in Healthy Subjects
A Phase 1 study testing NCO-48 Fumarate in people with Hepatitis B, run by Nucorion Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
The primary objective is to evaluate the safety and tolerability of single oral doses of NCO-48 Fumarate in healthy subjects. The secondary objectives are to evaluate the pharmacokinetic (PK) profile of NCO-48 Fumarate and its active metabolite, tenofovir (TFV), in healthy subjects following single oral doses and to… Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B
- What is being tested?
- NCO-48 Fumarate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Mar 2020to 13 Oct 2020
- 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 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male or female subjects 21 to 65 years of age, inclusive.
- Female subjects of non-childbearing potential must be surgically sterile or postmenopausal, defined as spontaneous amenorrhea for at least 2 years with follicle-stimulating hormone (FSH) in the post-menopausal range at the Screening Visit.
- Sexually active female subjects of childbearing potential (ie, ovulating, pre-menopausal, and not surgically sterile) with male partners or sexually active male subjects with female partners must agree to use a medically accepted contraceptive regimen during their participation in the study and for 90 days after the last dose of study drug.
- Male subjects must agree to abstain from sperm donation through 90 days after administration of the last dose of study drug.
- Body mass index (BMI) within the range of 18.5 to 30.0 kg/m2, inclusive, and body weight >45 kg.
- Able to communicate effectively with the study personnel.
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- Generally good health based upon the results of medical history, physical examination, vital signs, laboratory profile, and a 12-lead ECG, as judged by the Investigator.
- Nonsmokers, defined as not having smoked in the past 3 months prior to study drug administration.
- Willing and able to understand and comply with study procedures and restrictions, including confinement to the study site and consumption of study meals, and provide written informed consent according to institutional and regulatory guidelines.
- Estimated glomerular filtration rate >60 mL/min/1.73 m2 calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration formula.
Who cannot join
- Females who are pregnant or breastfeeding or planning to become pregnant during the study.
- History or presence of asthma or other clinically significant pulmonary disease, thyroid disease (hypo- or hyperthyroidism), hepatitis (except for resolved hepatitis A), or other liver disease.
- Have any disease or condition (medical or surgical) that, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous systems; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of study drug or would place the subject at increased risk.
- Liver transaminase levels (aspartate aminotransferase or alanine aminotransferase) >10% of the upper limit of normal, or presence of other abnormal laboratory values which are considered clinically significant at the Screening Visit or admission to study site (Day -1).
- Positive screening for hepatitis B (hepatitis B surface antigen), hepatitis C (hepatitis C antibody), or HIV (anti-HIV-1/2).
- Has used any other investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug.
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- Use of any of the following:
- Prescription drugs, other than topical products without significant systemic absorption, use of thyroid medication or hormone replacement therapy for at least 6 months, and hormonal contraceptives, within 14 days or 5 half lives (whichever is longer) prior to the first dose of study drug.
- Natural health products should be restricted within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
- Over-the-counter products and non-prescription drugs other than topical products without significant systemic absorption and/or hormone replacement therapy, within 7 days prior to the first dose of study drug, with the exception of the use of acetaminophen, which is allowed up to 1 g daily up to 24 hours prior to admission to the study site, then prohibited until after the last protocol-specified blood sample.
- Depot injection or implant of any drug (other than hormonal contraceptives) within 3 months prior to the first dose of study drug.
- Substances known to be strong inhibitors or inducers of cytochrome P450 enzymes within 14 days prior to the first dose of study drug through the last study visit.
- Unwilling to refrain from consumption of alcohol within 48 hours prior to each dose administration and during any inpatient period.
- Positive urine drug screen, positive alcohol breath test, and/or positive cotinine test at the Screening Visit or upon admission to the study site.
- History of alcohol abuse within 1 year prior to the Screening Visit or regular use of alcohol within 6 months prior to the Screening Visit.
- Illicit drug use (use of soft drugs [such as marijuana] within 3 months prior to the Screening Visit or hard drugs within 1 year prior to the Screening Visit), significant mental illness, physical dependence on any opioid, or any history of drug abuse or addiction.
- Inadequate venous access.
- Recently donated plasma (500 mL) within 7 days prior to study drug administration.
- Hemoglobin <128 g/L (males) or <115 g/L (females) and hematocrit <0.36 L/L (males) or <0.32 L/L (females) at the Screening Visit.
- History of photosensitivity while on medication.
- Deemed by the Investigator, after reviewing medical and psychiatric history, physical examination, or laboratory tests, to be unsuitable for any other reason that may either place the subject at increased risk during participation or interfere with the interpretation of the study outcomes.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medpace Clinical Pharmacology Unit
Cincinnati, Ohio, 45227
About this study
Official title: Double-Blind, Placebo-Controlled, Randomized, Ascending Single Oral Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of NCO-48 Fumarate in Healthy Subjects
The primary objective is to evaluate the safety and tolerability of single oral doses of NCO-48 Fumarate in healthy subjects. The secondary objectives are to evaluate the pharmacokinetic (PK) profile of NCO-48 Fumarate and its active metabolite, tenofovir (TFV), in healthy subjects following single oral doses and to evaluate the effect of food on the PK of a 30 mg dose of NCO-48 Fumarate in healthy subjects.
Read the detailed description
This is a first-in-human, double-blind, placebo-controlled, randomized, ascending single oral dose study. NCO-48 Fumarate will be assessed in healthy subjects (6 groups of 8 subjects each). Subjects will receive a single oral dose of NCO-48 Fumarate or placebo capsules in 1 or 2 periods, depending on the dose group, under fasting conditions (unless otherwise indicated) and will be followed for a 1-week observation period. Safety assessments will be performed and NCO-48 Fumarate and TFV PK will be assessed. The planned doses for this study are 2, 10, 30, 60, 120, and 240 mg. Each group of 8 subjects (Groups 1 to 6) will be randomized in a 3:1 ratio to receive either NCO-48 Fumarate or placebo (6 subjects to receive active drug and 2 subjects to receive placebo) as a single dose on Day 1 of Period 1 in the fasted state. A preliminary assessment of food effect will be conducted in Group 3. Subjects in Group 3 will receive study drug in Period 1 under fasted conditions and return after a minimum of 14 days to receive study drug under fed conditions. There will be a Screening Period of up to 30 days. All subjects (Periods 1 and 2) will be observed through the morning of Day 3 (48-hour post-dose assessment). Safety assessments and NCO-48 Fumarate and TFV PK sample collection (blood and urine) will occur during this time. Subjects will be discharged from the study site after the 48 hour assessments and return to the study site on Days 5 and 7 (final visit) for follow-up procedures. After the Day 7 follow-up procedures for each group, evaluation of all safety and tolerability data collected during the period, and evaluation of any available PK data, the dose for the next group of subjects will be determined by the Safety Monitoring Panel (SMP).
- Conditions
- Hepatitis B
- Being tested
- NCO-48 Fumarate, Placebo
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NCO-48 FumarateDrug
NCO-48 Fumarate
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| NCO-48 Fumarate | Experimental | NCO-48 Fumarate Receives: Drug: NCO-48 Fumarate |
| Placebo | Placebo comparator | Placebo Comparator Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of all Adverse Events graded according to the Common Terminology Criteria for Adverse Events (CTCAE)
An adverse event is defined as any untoward medical occurrence in a clinic investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. The severity of all adverse events will be graded according to the CTCAE version 4.0 from dosing until 30 days post dose.
Measured: 30 days
Secondary outcomes (4)
NCO-48 Fumarate Area Under the Concentration-Time Curve (AUC)
Blood samples are to be collected at designated time points for the determination of the NCO-48 Fumarate AUC
Measured: 7 days
NCO-48 Fumarate Maximum Plasma Concentration (Cmax)
Blood samples are to be collected at designated time points for the determination of the NCO-48 Fumarate Cmax.
Measured: 7 days
TFV Area under the Concentration-Time Curve (AUC)
Blood samples are to be collected at designated time points for the determination of TFV AUC .
Measured: 7 days
TFV Maximum Plasma Concentration (Cmax)
Blood samples are to be collected at designated time points for the determination of the TFV Cmax.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start18 Mar 2020
- Primary completion3 Aug 2020
- Study completion13 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nucorion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ligand Pharmaceuticals, Medpace, Inc.
- Responsible party
- Sponsor
- Investigators
- Leela Vrishabhendra, MD, Principal investigator, Medpace Clinical Pharmacology Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04309526
- Sponsor's protocol ID
- NCO48F-01
- Status last verified
- Nov 2020
- First submitted
- 11 Mar 2020
- Last updated
- 3 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind, Placebo-Controlled, Randomized, Ascending Single Oral Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of NCO-48 Fumarate in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04309526
- Acronym / sponsor ID
- NCO48F-01
- Conditions
- Hepatitis B
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Nucorion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Ligand Pharmaceuticals, Medpace, Inc.
- Study start
- 18 Mar 2020 (actual)
- Primary completion
- 3 Aug 2020 (actual)
- Study completion
- 13 Oct 2020 (actual)
- First posted
- 16 Mar 2020 (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.
The primary objective is to evaluate the safety and tolerability of single oral doses of NCO-48 Fumarate in healthy subjects. The secondary objectives are to evaluate the pharmacokinetic (PK) profile of NCO-48 Fumarate and its active metabolite, tenofovir (TFV), in healthy subjects following single oral doses and to evaluate the effect of food on the PK of a 30 mg dose of NCO-48 Fumarate in healthy subjects.
Detailed description
This is a first-in-human, double-blind, placebo-controlled, randomized, ascending single oral dose study. NCO-48 Fumarate will be assessed in healthy subjects (6 groups of 8 subjects each). Subjects will receive a single oral dose of NCO-48 Fumarate or placebo capsules in 1 or 2 periods, depending on the dose group, under fasting conditions (unless otherwise indicated) and will be followed for a 1-week observation period. Safety assessments will be performed and NCO-48 Fumarate and TFV PK will be assessed. The planned doses for this study are 2, 10, 30, 60, 120, and 240 mg. Each group of 8 subjects (Groups 1 to 6) will be randomized in a 3:1 ratio to receive either NCO-48 Fumarate or placebo (6 subjects to receive active drug and 2 subjects to receive placebo) as a single dose on Day 1 of Period 1 in the fasted state. A preliminary assessment of food effect will be conducted in Group 3. Subjects in Group 3 will receive study drug in Period 1 under fasted conditions and return after a minimum of 14 days to receive study drug under fed conditions. There will be a Screening Period of up to 30 days. All subjects (Periods 1 and 2) will be observed through the morning of Day 3 (48-hour post-dose assessment). Safety assessments and NCO-48 Fumarate and TFV PK sample collection (blood and urine) will occur during this time. Subjects will be discharged from the study site after the 48 hour assessments and return to the study site on Days 5 and 7 (final visit) for follow-up procedures. After the Day 7 follow-up procedures for each group, evaluation of all safety and tolerability data collected during the period, and evaluation of any available PK data, the dose for the next group of subjects will be determined by the Safety Monitoring Panel (SMP).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NCO-48 Fumarate | Experimental | Drug: NCO-48 FumarateNCO-48 Fumarate |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo Comparator |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Healthy male or female subjects 21 to 65 years of age, inclusive.
- Female subjects of non-childbearing potential must be surgically sterile or postmenopausal, defined as spontaneous amenorrhea for at least 2 years with follicle-stimulating hormone (FSH) in the post-menopausal range at the Screening Visit.
- Sexually active female subjects of childbearing potential (ie, ovulating, pre-menopausal, and not surgically sterile) with male partners or sexually active male subjects with female partners must agree to use a medically accepted contraceptive regimen during their participation in the study and for 90 days after the last dose of study drug.
- Male subjects must agree to abstain from sperm donation through 90 days after administration of the last dose of study drug.
- Body mass index (BMI) within the range of 18.5 to 30.0 kg/m2, inclusive, and body weight >45 kg.
Key exclusion criteria (21 listed)
- Females who are pregnant or breastfeeding or planning to become pregnant during the study.
- History or presence of asthma or other clinically significant pulmonary disease, thyroid disease (hypo- or hyperthyroidism), hepatitis (except for resolved hepatitis A), or other liver disease.
- Have any disease or condition (medical or surgical) that, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous systems; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of study drug or would place the subject at increased risk.
- Liver transaminase levels (aspartate aminotransferase or alanine aminotransferase) >10% of the upper limit of normal, or presence of other abnormal laboratory values which are considered clinically significant at the Screening Visit or admission to study site (Day -1).
- Positive screening for hepatitis B (hepatitis B surface antigen), hepatitis C (hepatitis C antibody), or HIV (anti-HIV-1/2).
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 |
|---|---|---|
| NCO-48 FumarateNCO-48 Fumarate | Drug | NCO-48 Fumarate |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Severity of all Adverse Events graded according to the Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: 30 days
An adverse event is defined as any untoward medical occurrence in a clinic investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. The severity of all adverse events will be graded according to the CTCAE version 4.0 from dosing until 30 days post dose.
4 secondary outcomes
NCO-48 Fumarate Area Under the Concentration-Time Curve (AUC)
Time frame: 7 days
NCO-48 Fumarate Maximum Plasma Concentration (Cmax)
Time frame: 7 days
TFV Area under the Concentration-Time Curve (AUC)
Time frame: 7 days
TFV Maximum Plasma Concentration (Cmax)
Time frame: 7 days
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 3 Nov 2020.
- Individual participant dataSharing planned: No
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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.
Leela Vrishabhendra, MD principal investigator
Medpace Clinical Pharmacology Unit
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 NCO-48 Fumarate in people with Hepatitis B, run by Nucorion Pharmaceuticals, Inc. at 1 site in United States.
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 10 inclusion and 21 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 3 Nov 2020. 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 United States. 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?
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?
Severity of all Adverse Events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) (time frame: 30 days). 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 3 Nov 2020.