Cystic FibrosisPhase 1(SNO-9)NCT02934139
MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Cavosonstat (N91115) in Healthy Subjects (SNO-9)
A Phase 1 study testing Cavosonstat in people with Cystic Fibrosis, run by Nivalis Therapeutics, Inc. at 1 site in United States.
Trial summary
The present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Cavosonstat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to Jan 2017
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent
- Healthy, determined at the screening medical evaluation (including but not limited to medical history, physical examination, and clinical laboratory evaluations)
- Male or female, between 18 and 55 years of age, inclusive at screening
- Caucasian (as reported by patient)
- The following applies to female subjects:
- Negative serum pregnancy test (for women of child-bearing potential) at screening and negative urine pregnancy at Day -1
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- Willing to use at least 1 highly effective method of birth control (excluding hormonal contraceptives) after signing consent, including abstinence which must be in use from the time of consent through the 30 days after completing the double-blind study drug
- The following applies to male subjects:
- Agrees to use a condom or abstinence, and agrees to refrain from sperm donation from date of informed consent signing through the 30 days after completing the double-blind study drug or
- Has documentation of azoospermia or vasectomy
- Non-smoker (or other nicotine user) as determined by history (no nicotine use over the past 6 months) and a negative cotinine test at screening and Day -1
- Body mass index between 18 and 32 kg/m2 inclusive at screening, and weighs at least 50 kg at screening
- No clinically significant vital sign findings including no clinically significant abnormal findings related to their systolic or diastolic BP at screening or prior to dosing on Day 1, per the investigator's judgment.
- No clinically significant abnormal findings in 12-lead ECG, per the investigator's judgment, at screening or prior to dosing on Day 1
- No clinically significant abnormalities in hematology, clinical chemistry, and urinalysis results that would interfere with the study assessments at screening
Who cannot join
- History of any illness or condition that in the opinion of the investigator could confound the results of the study or pose additional risk when administered IMP, such as clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the investigator or designee
- Concurrent disease or condition, that, in the opinion of the investigator, would make the subject unsuitable for participation in the clinical study
- Any of the following findings on a 12-lead ECG done at screening:
- HR < 45 bpm or > 95 bpm
- QTcF > 450 msec for males and >470 msec for females
- PR > 220 msec
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- QRS duration > 110 msec
- ST segment abnormal
- T-wave changes
- QRS, ST, or T-wave findings making it technically difficult to determine the QT intervals
- Any of the following on 24-hour ambulatory ECG (Holter) monitoring at screening:
- Supraventricular ectopy i. Singlets: > 200 / 24 hours ii. Couplets: > 20 / hour iii. Runs: > 10 beats b. Ventricular ectopy i. Unifocal singlets: > 100 / 24 hours ii. Unifocal couplets: > 20 / hour iii. Complex of multifocal singlets: > 50 / 24 hours iv. Complex of multifocal couplets: > 10 / 24 hours v. Any Run (ventricular tachycardia) c. Heart rate i. < 40 bpm for 1 minute while awake ii. < 35 bpm for 3 minutes while asleep iii. > 120 bpm for 3 minutes (when not exercising) iv. Pauses > 2000 msec d. 2nd or 3rd degree AV block e. Intraventricular conduction delay (IVCD) with QRS duration > 120 msec or right bundle branch block (RBBB) or left buddle branch block (LBBB) other than rare RBBB f. Atrial flutter or atrial fibrillation regardless of rate
- Disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs as determined by the investigator
- History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening
- Positive alcohol test at screening or Day -1.
- Positive drug test (including but not limited to cocaine, amphetamines, barbiturates, opiates, benzodiazepines) at screening or Day -1.
- A positive drug test for cannabinoids at screening will be allowed if the subject agrees to abstain from use of all forms of cannabinoids during screening and throughout the study and has a negative test at Day -1
- Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.
- Unwilling to limit consumption of coffee and caffeine-containing foods and beverages from Day -1 until discharge on Day 8.
- Unwilling to avoid use of alcohol or alcohol-containing foods, medications, or beverages from Day -1 until discharge on Day 8.
- Subject has donated blood (> 500 mL) or blood products within 56 days prior to Day -1.
- Use of vitamins from Day -7 until end-of-study follow up call, and use of over-thecounter (OTC) medications, prescription medications, or herbal remedies from Day - 14 until end-of-study follow-up call. By exception, acetaminophen ≤ 1000 mg/day is permitted except within 48 hours prior to Day -1. Hormone replacement therapy (HRT) and hormonal contraception is allowed throughout the study. The Medical Monitor and Principal Investigator may allow certain OTC medications by exception if they are not likely to affect study conduct and output.
- Use of an investigational drug within 30 days prior to Day 1 dosing.
- Unwilling to abstain from vigorous exercise from Day -1 until discharge on Day 8.
- Problems understanding the protocol requirements, instructions and study related restrictions, the nature, scope, and possible consequences of the clinical study.
- Unlikely to comply with the protocol requirements, instructions, and study related restrictions; e.g., uncooperative attitude, unavailable for follow-up call, and/or improbability of completing the clinical study.
- History of bleeding disorders (i.e., severe hemorrhage, melena, rectal bleeding, nosebleeds, bruising, etc.).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of N91115 in Healthy Subjects
The present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.
Read the detailed description
This study will assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.
Approximately 5 ascending cohorts are planned with approximately 8 subjects per cohort (6 active, 2 placebo). Each subject will undergo screening (Day -28 to Day -2) and, if eligible, return to the unit on Day -1 when eligibility will be reconfirmed.
Eligible subjects will be randomized in a 3:1 ratio to receive investigational medicinal product (IMP) N91115 (daily [QD] or every 12 hours [Q12H]) or matching placebo (QD or Q12H) for 7 days and will be followed for safety while housed in the clinical research unit (CRU) until discharge on Day 8. Pharmacokinetics will be followed from Study Day 1 through the morning of Study Day 8. The subjects will be discharged from the CRU and complete the post treatment withdrawal phase, including a follow-up phone call on Day 15.
- Conditions
- Cystic Fibrosis
- Being tested
- Cavosonstat, Placebo
- Keywords
- N91115, Cavosonstat, Healthy Volunteer
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CavosonstatDrug
Also called N91115
CFTR modulator that stabilizes CFTR
PlaceboOther
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Cavosonstat (N91115) 400 mg | Experimental | Every 12 hour oral dosing of N91115 for 7 days Receives: Drug: Cavosonstat |
| Cavosonstat (N91115) 600 mg | Experimental | Every 12 hour oral dosing of N91115 for 7 days Receives: Drug: Cavosonstat |
| Cavosonstat (N91115) 1200 mg | Experimental | Once daily oral dosing of N91115 for 7 days Receives: Drug: Cavosonstat |
| Cavosonstat (N91115) 800 mg | Experimental | Every 12 hour oral dosing of N91115 for 7 days Receives: Drug: Cavosonstat |
| Placebo | Placebo comparator | Matched placebo. Oral dosing every 12 hour or once daily for 7 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Safety assessments based on clinical evaluations, laboratory assessments, and adverse events
Measured: 14 days
Secondary outcomes (10)
Pharmacokinetic parameters of N91115 and metabolites (Amount of analyte excreted in the urine [Ae])
Pharmacokinetic parameter of N91115 and metabolites will be measured in urine.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (% analyte excreted in the urine [Fe])
Pharmacokinetic parameter of N91115 and metabolites will be measured in urine.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (area under the curve [AUC])
Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (maximum concentration [Cmax])
Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (clearance [CL])
Pharmacokinetic parameter of N91115 and metabolites will be measured in urine and plasma.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (accumulation index [Racc])
Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (Terminal elimination half-life [t1/2])
Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (time of maximum concentration [Tmax])
Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (metabolite to parent exposure ratio [M/P ratio])
Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measured: 7 days
Pharmacokinetic parameters of N91115 and metabolites (terminal elimination rate constant [lambda z])
Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
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 posted14 Oct 2016 (estimated)
- Study startOct 2016
- Primary completionDec 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nivalis Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Williams, MD, Principal investigator, Davita Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02934139
- Sponsor's protocol ID
- N91115-1HS-08
- Acronym
- (SNO-9)
- Status last verified
- Jan 2017
- First submitted
- 10 Oct 2016
- Last updated
- 31 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of N91115 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02934139
- Acronym / sponsor ID
- (SNO-9) / N91115-1HS-08
- Conditions
- Cystic Fibrosis
- Keywords
- N91115, Cavosonstat, Healthy Volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Nivalis Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2016
- Primary completion
- Dec 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 14 Oct 2016 (estimated)
- 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 present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.
Detailed description
This study will assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.
Approximately 5 ascending cohorts are planned with approximately 8 subjects per cohort (6 active, 2 placebo). Each subject will undergo screening (Day -28 to Day -2) and, if eligible, return to the unit on Day -1 when eligibility will be reconfirmed.
Eligible subjects will be randomized in a 3:1 ratio to receive investigational medicinal product (IMP) N91115 (daily [QD] or every 12 hours [Q12H]) or matching placebo (QD or Q12H) for 7 days and will be followed for safety while housed in the clinical research unit (CRU) until discharge on Day 8. Pharmacokinetics will be followed from Study Day 1 through the morning of Study Day 8. The subjects will be discharged from the CRU and complete the post treatment withdrawal phase, including a follow-up phone call on Day 15.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cavosonstat (N91115) 400 mg | Experimental | Drug: CavosonstatEvery 12 hour oral dosing of N91115 for 7 days |
| Cavosonstat (N91115) 600 mg | Experimental | Drug: CavosonstatEvery 12 hour oral dosing of N91115 for 7 days |
| Cavosonstat (N91115) 1200 mg | Experimental | Drug: CavosonstatOnce daily oral dosing of N91115 for 7 days |
| Cavosonstat (N91115) 800 mg | Experimental | Drug: CavosonstatEvery 12 hour oral dosing of N91115 for 7 days |
| Placebo | Placebo comparator | Other: PlaceboMatched placebo. Oral dosing every 12 hour or once daily for 7 days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Written informed consent
- Healthy, determined at the screening medical evaluation (including but not limited to medical history, physical examination, and clinical laboratory evaluations)
- Male or female, between 18 and 55 years of age, inclusive at screening
- Caucasian (as reported by patient)
- The following applies to female subjects:
Key exclusion criteria (27 listed)
- History of any illness or condition that in the opinion of the investigator could confound the results of the study or pose additional risk when administered IMP, such as clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the investigator or designee
- Concurrent disease or condition, that, in the opinion of the investigator, would make the subject unsuitable for participation in the clinical study
- Any of the following findings on a 12-lead ECG done at screening:
- Any of the following on 24-hour ambulatory ECG (Holter) monitoring at screening:
- Disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs as determined by the investigator
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 |
|---|---|---|
| CavosonstatAlso: N91115CFTR modulator that stabilizes CFTR | Drug | Cavosonstat (N91115) 1200 mg, Cavosonstat (N91115) 400 mg, Cavosonstat (N91115) 600 mg, Cavosonstat (N91115) 800 mg |
| PlaceboMatched placebo | Other | Placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 14 days
Safety assessments based on clinical evaluations, laboratory assessments, and adverse events
10 secondary outcomes
Pharmacokinetic parameters of N91115 and metabolites (Amount of analyte excreted in the urine [Ae])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (% analyte excreted in the urine [Fe])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (area under the curve [AUC])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (maximum concentration [Cmax])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (clearance [CL])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (accumulation index [Racc])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (Terminal elimination half-life [t1/2])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (time of maximum concentration [Tmax])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (metabolite to parent exposure ratio [M/P ratio])
Time frame: 7 days
Pharmacokinetic parameters of N91115 and metabolites (terminal elimination rate constant [lambda z])
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 31 Jan 2017.
- 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.
Robert Williams, MD principal investigator
Davita Clinical Research
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 Cavosonstat in people with Cystic Fibrosis, run by Nivalis Therapeutics, 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 15 inclusion and 27 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 31 Jan 2017. 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?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: 14 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 31 Jan 2017.