Healthy VolunteersPhase 1NCT04896632
Study of Safety, Tolerability, and Pharmacokinetics of INE963 in Healthy Participants
A Phase 1 study testing INE 963 in people with Healthy Volunteers, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
Trial summary
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of single ascending doses and multiple doses of INE963 given orally in healthy participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- INE 963
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 May 2021to 24 Nov 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- Healthy male and female participants 18 to 55 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- At screening and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the supine position Supine vital signs should be within the following ranges:
- oral body temperature between 35.0 - 37.5 °C
- systolic blood pressure, 90 - 140 mm Hg
- diastolic blood pressure, 50 - 90 mm Hg
Show all 9Show fewer
- pulse rate, 40 - 90 bpm If vital signs are outside these ranges, the investigator may obtain up to 2 additional readings so that a total of up to 3 consecutive assessments are made. At least the last reading must be within the ranges provided above in order for the participant to qualify.
- Participants must weigh at least 50 kg at screening and baseline to participate in the study, and must have a body mass index (BMI) within the range of 18.0 - 32.0 kg/m2. BMI = Body weight (kg) / [Height (m)]2
- Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Who cannot join
- History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes
- Significant illness which has not resolved within two (2) weeks prior to initial dosing.
- Recent (within the last three years of screening) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).
- Recent (within the last three years of screening) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
- Known history or current clinically significant arrhythmias.
- Known family history or known presence of long QT syndrome.
Show all 42Show fewer
- A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening and/or baseline:
- PR > 220 msec
- QRS complex > 120 msec
- RR >1.5 seconds
- QTcF > 450 msec (males)
- QTcF > 460 msec (females)
- History of immunodeficiency diseases, including a positive HIV test result.
- Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive HBV surface antigen (HBsAg) test, excludes a participant. Participants with a positive HCV antibody test should have HCV RNA levels measured. Participants with positive (detectable) HCV RNA should be excluded.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years of screening, regardless of whether there is evidence of local recurrence or metastases.
- Donation or loss of 450 mL or more of blood within eight weeks prior to initial dosing, or longer if required by local regulation.
- Plasma donation (> 450 mL) within 8 weeks prior to first dosing.
- Any clinically significant hematology parameters outside normal ranges at screening and/or baseline. Participants with neutrophils <1.5 x 109/L should be excluded.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant in case of participation in the study. The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence of any of the following at screening or baseline:
- Inflammatory bowel disease, peptic ulcers, gastrointestinal including rectal bleeding;
- Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
- Pancreatic injury or pancreatitis;
- Liver disease or liver injury as indicated by abnormal liver function tests (as defined below). ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase and serum bilirubin will be tested.
- Any single parameter of ALT, AST, GGT, alkaline phosphatase or serum bilirubin must not exceed the upper limit of normal (ULN)
- History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN and/or urea values, or abnormal urinary constituents (e.g. albuminuria).
- Evidence of urinary obstruction or difficulty in voiding at screening.
- Use of any prescription drugs, herbal supplements, prescribed medicinal use of cannabis/marijuana, within four weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two weeks prior to initial dosing. If needed, (i.e. an incidental and limited need) paracetamol/acetaminophen is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF.
- Smokers (use of tobacco/nicotine products 1 week prior to screening). Urine cotinine levels will be measured during screening and at each baseline for all participants. Smokers will be defined as any participant who reports tobacco use and/or who has a urine cotinine ≥ 200 ng/mL.
- History of drug abuse or unhealthy alcohol use# within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and at baseline. #Unhealthy alcohol use is defined as a history of, or current alcohol misuse/abuse, defined as " >21 units for males and >14 units for females in the same week."
- History of recreational cannabis use within four weeks prior to dosing, or evidence of such use as indicated by the laboratory assays conducted during screening and baseline. This exclusion criterion applies even if cannabis use is legalized where the site is located. Any prescribed, medicinal use of cannabis is to be handled according to the prescription drug usage criteria defined above.
- Pregnant or nursing (lactating) women.
- Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 5 half-lives or 14 days after stopping investigational drug, whichever is longer. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner for 5 half-lives or 14 days after last dose, whichever is longer. In addition, male participants should not donate sperm for the time period specified above. Additionally, the female partners of male participants should also use an effective method of contraception.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. Women are considered post-menopausal or not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or total hysterectomy at least six weeks before screening. In the case of oophorectomy alone, only when the reproductive status of the women has been confirmed by follow-up hormone level assessment if she is considered not of child-bearing potential. Refer to Section 8.6.6 Pregnancy and Assessments of Fertility.
- Use of other investigational drugs at the time of enrollment or within 90 days of first dose in this study, or within 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations.
- Participants who do not have suitable veins for multiple venipuncture cannulation as assessed by the investigator of delegate at screening
- Participants in the food effect cohort: history of cholecystectomy or gall stones
- Presence or history of clinically significant allergy requiring treatment as judged by the investigator. Hay fever is allowed unless it is active.
- Evidence of an active infection, including COVID-19
- Participants who are immediate family members to other participants
- Participants who have previously participated in another cohort for this study
- Known or current history of hemoglobinopathies including sickle cell disease
- Intake of grapefruit or grapefruit juice within 14 days prior to initial dosing. No grapefruit or grapefruit juice is allowed until 7 days following the last dose
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Novartis Investigative Site
Mere Way, Nottingham, NG11 6JS
About this study
Official title: A Randomized, Participant- and Investigator-blinded, Placebo-controlled, Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of INE963 in Healthy Participants
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of single ascending doses and multiple doses of INE963 given orally in healthy participants.
Read the detailed description
This is a randomized, participant- and investigator-blinded, placebo-controlled, single ascending and multiple oral dose study in healthy participants. The study consisted of two parts:
- Part A was a single ascending dose (SAD) study with 6 planned cohorts: (A1, A2, A4, A5, A6 and A7) of 8 participants each and 1 cohort (A3) with 10 participants, as randomization ratio 4:1 was originally planned due to the food effect cohort. There was also an optional cohort of 8 subjects (A8).
- Part B was a multiple dose (MAD) study with 2 planned cohort of 9 participants (B1 and B2; randomization ratio 2:1). There was also an optional cohort of 9 subjects (B3).
Cohort B2 and Optional Cohorts A8 and B3 were not dosed since the study was terminated early as per joint decision between the Principal Investigator and the Sponsor. Importantly, the decision to terminate the study early was not taken as a consequence of any safety concerns seen with INE963 administration in healthy volunteers.
- Conditions
- Healthy Volunteers
- Being tested
- INE 963, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INE 963Drug
Part A: Single ascending dose with 7 planned cohorts> Part B: multiple dose with 2 planned cohort q24x3 days
PlaceboOther
Part A: single ascending dose with 7 planned cohorts. Part B: multiple dose with 2 planned q24x3 days.
| Study group | Role | What they receive |
|---|---|---|
| INE963 | Experimental | Part A is a single ascending dose (SAD) study with 7 planned cohorts Part B is a multiple dose (MD) study with 2 planned cohort q24h x 3 day of either INE963 or placebo Receives: Drug: INE 963 |
| Placebo group | Placebo comparator | Part A is a single ascending dose (SAD) study with 7 planned cohorts Part B is a multiple dose (MD) study with 2 planned cohort q24h x 3 day of either INE963 or placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects with Significant Clinical Safety Labs, reporting SAEs and AEs and ECG findings
Number of Subjects with Significant Clinical Safety Labs, reporting SAEs and AEs and ECG findings, as judged by investigator at each dose escalation review meetings
Measured: Dose escalation (21 days)
Secondary outcomes (11)
INE963 pharmacokinetic parameters AUC in SAD Part
INE963 pharmacokinetic parameters (AUC) in SAD Part at specified timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters Tmax in SAD Part
INE963 pharmacokinetic parameters in SAD Part (Tmax) at the specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters Cmax in SAD Part
INE963 pharmacokinetic parameters (Cmax) in SAD Part at specified timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters Vz/F in SAD Part
INE963 pharmacokinetic parameters in SAD Part (Vz/F) at the specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters T1/2 in SAD Part
INE963 pharmacokinetic parameters in SAD Part (T1/2) at the specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters in MAD Part (AUC)
INE963 pharmacokinetic parameters in MAD Part (AUC) measured at specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (Cmax)
INE963 pharmacokinetic parameters in MAD Part (Cmax) measured at specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (Tmax)
INE963 pharmacokinetic parameters in MAD Part (Tmax) measured at specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (Vz/F)
INE963 pharmacokinetic parameters in MAD Part (Vz/F) measured at specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (T1/2)
INE963 pharmacokinetic parameters in MAD Part (T1/2) measured at specific timepoints
Measured: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
Baseline AAG concentration
Alpha-1- acid glycoprotein (AAG) level will be taken at baseline for Part A and Part b.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2021
- Study start13 May 2021
- Primary completion24 Nov 2022
- Study completion24 Nov 2022
Why it stopped: Sponsor's decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04896632
- Sponsor's protocol ID
- CINE963A02101
- Status last verified
- Sep 2023
- First submitted
- 12 May 2021
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Participant- and Investigator-blinded, Placebo-controlled, Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of INE963 in Healthy Participants
- ClinicalTrials.gov ID
- NCT04896632
- Acronym / sponsor ID
- CINE963A02101
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision.
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 May 2021 (actual)
- Primary completion
- 24 Nov 2022 (actual)
- Study completion
- 24 Nov 2022 (actual)
- First posted
- 21 May 2021 (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 purpose of this study is to assess the safety, tolerability, and pharmacokinetics of single ascending doses and multiple doses of INE963 given orally in healthy participants.
Detailed description
This is a randomized, participant- and investigator-blinded, placebo-controlled, single ascending and multiple oral dose study in healthy participants. The study consisted of two parts:
- Part A was a single ascending dose (SAD) study with 6 planned cohorts: (A1, A2, A4, A5, A6 and A7) of 8 participants each and 1 cohort (A3) with 10 participants, as randomization ratio 4:1 was originally planned due to the food effect cohort. There was also an optional cohort of 8 subjects (A8).
- Part B was a multiple dose (MAD) study with 2 planned cohort of 9 participants (B1 and B2; randomization ratio 2:1). There was also an optional cohort of 9 subjects (B3).
Cohort B2 and Optional Cohorts A8 and B3 were not dosed since the study was terminated early as per joint decision between the Principal Investigator and the Sponsor. Importantly, the decision to terminate the study early was not taken as a consequence of any safety concerns seen with INE963 administration in healthy volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INE963 | Experimental | Drug: INE 963Part A is a single ascending dose (SAD) study with 7 planned cohorts Part B is a multiple dose (MD) study with 2 planned cohort q24h x 3 day of either INE963 or placebo |
| Placebo group | Placebo comparator | Other: PlaceboPart A is a single ascending dose (SAD) study with 7 planned cohorts Part B is a multiple dose (MD) study with 2 planned cohort q24h x 3 day of either INE963 or placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Written informed consent must be obtained before any assessment is performed.
- Healthy male and female participants 18 to 55 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- At screening and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the supine position Supine vital signs should be within the following ranges:
- Participants must weigh at least 50 kg at screening and baseline to participate in the study, and must have a body mass index (BMI) within the range of 18.0 - 32.0 kg/m2. BMI = Body weight (kg) / [Height (m)]2
- Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Key exclusion criteria (42 listed)
- History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes
- Significant illness which has not resolved within two (2) weeks prior to initial dosing.
- Recent (within the last three years of screening) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).
- Recent (within the last three years of screening) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
- Known history or current clinically significant arrhythmias.
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 |
|---|---|---|
| INE 963Part A: Single ascending dose with 7 planned cohorts> Part B: multiple dose with 2 planned cohort q24x3 days | Drug | INE963 |
| PlaceboPart A: single ascending dose with 7 planned cohorts. Part B: multiple dose with 2 planned q24x3 days. | Other | Placebo group |
Primary outcome
Number of Subjects with Significant Clinical Safety Labs, reporting SAEs and AEs and ECG findings
Time frame: Dose escalation (21 days)
Number of Subjects with Significant Clinical Safety Labs, reporting SAEs and AEs and ECG findings, as judged by investigator at each dose escalation review meetings
11 secondary outcomes
INE963 pharmacokinetic parameters AUC in SAD Part
Time frame: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters Tmax in SAD Part
Time frame: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters Cmax in SAD Part
Time frame: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters Vz/F in SAD Part
Time frame: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters T1/2 in SAD Part
Time frame: Day 1, 2, 3, 4, 6, 8, 9, 12 and 16
INE963 pharmacokinetic parameters in MAD Part (AUC)
Time frame: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (Cmax)
Time frame: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (Tmax)
Time frame: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (Vz/F)
Time frame: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
INE963 pharmacokinetic parameters in MAD Part (T1/2)
Time frame: Day 1, 2, 3, 4, 6, 8, 10, 11, 14 and Day 18
Baseline AAG concentration
Time frame: Baseline
Results and safety
The study was stopped early (reason given: Sponsor's decision.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Individual participant dataSharing planned: No
Related trials for Healthy Volunteers
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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
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 INE 963 in people with Healthy Volunteers, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
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 9 inclusion and 42 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 28 Sep 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 United Kingdom. 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 was stopped early (reason given: Sponsor's decision.). Results are not available in the source record.
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 Subjects with Significant Clinical Safety Labs, reporting SAEs and AEs and ECG findings (time frame: Dose escalation (21 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 28 Sep 2023.