Pain, PostoperativePhase 1NCT04515953

A Phase I Dose-escalation Study of a Single Administration of Extended-Release Injectable Suspension (ND-340)

A Phase 1 study testing ND-340 and IV-PCA in people with Pain, Postoperative, run by Nang Kuang Pharmaceutical Co., Ltd. at 1 site in Taiwan.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record

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Trial summary

This study focused on ND-340 extended release injection suspension for patients undergoing total knee arthroplasty with a one-time nerve blockade to assess drug side effects, pharmacokinetics and the effect of pain relief after surgery. Read more about this study

Who is it for?: Ages 20 to 80 years
Conditions the study is for: Pain, Postoperative
What is being tested?: ND-340 and IV-PCA
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 1 siteTaiwan
Study dates: 15 Oct 2020to Jun 2026
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 20 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subject with age between 20 and 80 (inclusive) years old at the screening visit
With physician's order to undergo scheduled primary unilateral TKA
Female subject with childbearing potential must have a negative serum pregnancy test at the screening visit
Both male and female subjects with childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], and intrauterine devices) during the course of the study with their partners (excluding women who are not of childbearing potential and men who have been sterilized).
Able and willing to comply with all study visits and procedures
Able to speak, read, and understand the language of the informed consent form (ICF), study questionnaires, and other instruments used for collecting subject-reported outcomes, in order to enable accurate and appropriate responses to pain scales and other required study assessments
Willing and capable of providing written informed consent

Who cannot join

Body weight < 50 kilograms or a morbidly obese (body mass index ≥ 35kg/m2)
Subject with American Society of Anesthesiologists (ASA) physical status > 3 at the screening visit
Undergoing or is plan to undergo bilateral or revision total knee replacement
Previous contralateral TKA or open knee surgery on the knee being considered for TKA in this study within 1 year prior to screening. Prior arthroscopy at least 1 week prior to TKA is permitted.
Use of any of the following medications within the time specified before TKA
Use of any opioid within 24 hours or long-acting opioid within 3 days

Show all 29Show fewer

Use of any NSAID including selective COX-2 inhibitor within 3 days
Use of any selective serotonin reuptake inhibitors (SSRIs), gabapentin, pregabalin (LYRICA®), or duloxetine (CYMBALTA®) within 3 days
Use of monoamine oxidase inhibitors (MAOIs) within 14 days
Concurrent painful physical condition, diseases or concurrent surgery that may require analgesic treatment (such as NSAIDs or opioids) in the post-operative period for pain that is not strictly related to the surgery, and which may confound the post-operative assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery)
Pre-operative liver insufficiency as defined by liver function tests [i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin] ≥ 1.5 times the upper limit of normal (ULN) at the screening visit
Pre-operative renal insufficiency (creatinine clearance < 60 mL/min) at the screening visit
Known of active infection with HIV, HBV, or HCV at the screening visit
With abnormal ECG at screening and admission, which is not suitable to participate into this study as judged by the investigator before TKA
With abnormal results of sensory examination as judged by the investigator before TKA
Administration of an investigational drug within 30 days or 5 elimination half- lives of such investigational drug, whichever is longer, prior to study drug administration; or planned administration of another investigational product or procedure during the study period
Receiving other surgeries within 30 days prior to screening
Receiving blood transfusion within 30 days prior to screening
With a history of allergy or hypersensitivity to local anesthetics
Previous hypersensitivity to or contraindication to any of the pain-control agents planned for surgical or post-operative use in this study (i.e., morphine, bupivacaine, tramadol, and acetaminophen)
History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years prior to screening
Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that could interfere with study assessments or compliance in the opinion of the investigator
Current or historical evidence of any clinically significant disease or condition, especially terminal stage cancer, poorly controlled diabetic mellitus (i.e., HbA1c > 8%), or neurological disease that, in the opinion of the investigator, may increase the risk of study treatment and TKA, or complicate the subject's post-operative course or interfere with the determination of pain intensity related solely to the TKA
Subject with severe heart diseases (NYHA class-III and IV), with ischemic heart diseases (angina pectoris and myocardial infarction) and subject who underwent percutaneous transluminal coronary angioplasty (PTCA) or had treatments for coronary artery bypass graft within 6 months prior to screening
With pre-existed psychiatric or neurological deficits, which may compromise the neurological toxicity evaluations in this study by the investigator's judgment
With stroke within 1 year prior to screening
With bone cancer within 5 years prior to screening
Inability to understand or operate the PCA machine
Female subject who is breast-feeding, pregnant, or planning to become pregnant

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

Nang Kuang Pharmaceutical Co., LTD
Tainan, Taiwan (台灣), 712

Other trials in Taiwan

About this study

Official title: A Phase I Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of a Single Administration of Extended-Release Injectable Suspension (ND-340) as Post-operative Analgesia in Patients With Total Knee Arthroplasty (TKA)

Conditions: Pain, Postoperative
Being tested: ND-340, IV-PCA
Medical subject headings: Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ND-340Drug
ND-340: Subjects will receive a single administration of ND-340 at the specified dose in each arm after TKA.
IV-PCADrug
IV-PCA: Intravenous patient-controlled analgesia (IV-PCA), morphine, will be administered in subjects of control group after TKA for postoperative pain management as standard practice.

Study groups in NCT04515953
Study group	Role	What they receive
Control	Active comparator	Standard practice of pain management for post-TKA Receives: Drug: IV-PCA
ND-340	Experimental	ND-340 90mg~320mg at dose escalations Receives: Drug: ND-340

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
The AEs of special interest, including any symptom of local anesthetic systemic toxicity (LAST), cardiac events, neurologic events, and falls, will be analyzed by cohort.
Measured: up to 3 months
Cmax
Maximum Plasma Concentration of ND-340
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Tmax
Time of peak concentration of ND-340
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
AUC 0-t
Area under the plasma concentration versus time curve from zero to t of ND-340
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
AUC 0-∞
Area under the plasma concentration versus time curve from zero to infinity of ND-340
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
T1/2
Terminal half life of ND-340
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
CL/F
Clearance/Bioavailability of ND-340
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
λz
Terminal elimination rate constant
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Vz/F
Apparent volume of distribution during terminal phase after non-intravenous administration
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
MRT 0-∞
Mean residence time
Measured: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

Secondary outcomes (5)

Pain intensity
The pain assessment in subjects will be analyzed by each cohort. The AUC of NRS-R or NRS-A within 24 hours (AUCNRS-R, 0-24 or AUCNRS-A, 0-24), 56 hours (AUCNRS-R, 0-56 or AUCNRS-A, 0-56), 80 hours (AUCNRS-R, 0-80 or AUCNRS-A, 0-80), 104 hours (AUCNRS-R, 0-104 or AUCNRS-A, 0-104), 128 hours (AUCNRS-R, 0-128 or AUCNRS-A, 0-128), and 164 hours (AUCNRS-R, 0-164 or AUCNRS-A, 0-164) after TKA will be analyzed and score-time curves will be plotted graphically.
Measured: up to 1 week
The requirement for rescue pain medication
The requirement for rescuing pain medication will be analyzed by each cohort. Descriptive statistics will be used to analyze the percentage of subjects who use all IV-PCA morphine dose within 48 hours post-TKA or the percentage of subjects who use ULTRACET® within 7 days post-TKA, time period from the end of TKA to the first bolus dose of IV-PCA morphine or to the first use of ULTRACET® by cohort, the total amount of IV-PCA morphine administered within 48 hours post-TKA or the total amount of ULTRACET® administered within 7 days post-TKA.
Measured: up to 1 week
The ambulation distance
The ambulation distance as measured by six-minute walk test (6MWT) at baseline and subsequent visits, and the change from baseline will be summarized descriptively by cohorts.
Measured: up to 3 months
Range of motion of knee
The range of motion (ROM) of knee as measured by knee flexion and extension at baseline and subsequent visits, and the change from baseline will be summarized descriptively by cohorts.
Measured: up to 3 months
WOMAC
The quality of life (QoL) as measured by WOMAC Index at baseline and subsequent visits, and the change from baseline will be summarized descriptively by cohorts.
Measured: up to 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Oct 2020Jun 2026

First posted17 Aug 2020
Study start15 Oct 2020
Primary completionDec 2025 (estimated)
Study completionJun 2026 (estimated)

Why it stopped: pending

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Pain, PostoperativeStudies 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: Parallel groups
Model description: The first two arms of the placebo control and the 1st dose level ND-340 were randomly paralleled and then subsequently arms for ND-340 dose escalations.
Masking: None (open label)
Enrolment: 36 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04515953
Sponsor's protocol ID: QCR19001
Status last verified: Oct 2023
First submitted: 8 Jul 2020
Last updated: 9 Nov 2023
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pain, Postoperative trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of a Single Administration of Extended-Release Injectable Suspension (ND-340) as Post-operative Analgesia in Patients With Total Knee Arthroplasty (TKA)
ClinicalTrials.gov ID: NCT04515953
Acronym / sponsor ID: QCR19001
Conditions: Pain, Postoperative
Phase: Phase 1
Study type: Interventional
Recruitment status: SuspendedReason stopped: pending
Enrolment: 36 participants (estimated)
Lead sponsor: Nang Kuang Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: 15 Oct 2020 (actual)
Primary completion: Dec 2025 (estimated)
Study completion: Jun 2026 (estimated)
First posted: 17 Aug 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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: The first two arms of the placebo control and the 1st dose level ND-340 were randomly paralleled and then subsequently arms for ND-340 dose escalations.

Arm	Type	Receives
Control	Active comparator	Drug: IV-PCAStandard practice of pain management for post-TKA
ND-340	Experimental	Drug: ND-340ND-340 90mg~320mg at dose escalations

Who may qualify

Ages: 20 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Subject with age between 20 and 80 (inclusive) years old at the screening visit
With physician's order to undergo scheduled primary unilateral TKA
Female subject with childbearing potential must have a negative serum pregnancy test at the screening visit
Both male and female subjects with childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], and intrauterine devices) during the course of the study with their partners (excluding women who are not of childbearing potential and men who have been sterilized).
Able and willing to comply with all study visits and procedures

Key exclusion criteria (29 listed)

Body weight < 50 kilograms or a morbidly obese (body mass index ≥ 35kg/m2)
Subject with American Society of Anesthesiologists (ASA) physical status > 3 at the screening visit
Undergoing or is plan to undergo bilateral or revision total knee replacement
Previous contralateral TKA or open knee surgery on the knee being considered for TKA in this study within 1 year prior to screening. Prior arthroscopy at least 1 week prior to TKA is permitted.
Use of any of the following medications within the time specified before TKA

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
ND-340ND-340: Subjects will receive a single administration of ND-340 at the specified dose in each arm after TKA.	Drug	ND-340
IV-PCAIV-PCA: Intravenous patient-controlled analgesia (IV-PCA), morphine, will be administered in subjects of control group after TKA for postoperative pain management as standard practice.	Drug	Control

Primary outcome

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: up to 3 months
The AEs of special interest, including any symptom of local anesthetic systemic toxicity (LAST), cardiac events, neurologic events, and falls, will be analyzed by cohort.
Cmax
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Maximum Plasma Concentration of ND-340
Tmax
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Time of peak concentration of ND-340
AUC 0-t
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Area under the plasma concentration versus time curve from zero to t of ND-340
AUC 0-∞
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Area under the plasma concentration versus time curve from zero to infinity of ND-340
T1/2
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Terminal half life of ND-340
CL/F
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Clearance/Bioavailability of ND-340
λz
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Terminal elimination rate constant
Vz/F
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Apparent volume of distribution during terminal phase after non-intravenous administration
MRT 0-∞
Time frame: 0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour
Mean residence time

5 secondary outcomes

Pain intensity
Time frame: up to 1 week
The requirement for rescue pain medication
Time frame: up to 1 week
The ambulation distance
Time frame: up to 3 months
Range of motion of knee
Time frame: up to 3 months
WOMAC
Time frame: up to 3 months

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2023.

Related trials for Pain, Postoperative

Recruiting
Radiofrequency Ablation for the Treatment of Post-knee Arthroplasty Chronic Pain.
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Recruiting
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RecruitingPhase 4
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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.

Chih-Peng Lin principal investigator

National Taiwan University Hospital

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 ND-340 and IV-PCA in people with Pain, Postoperative, run by Nang Kuang Pharmaceutical Co., Ltd. at 1 site in Taiwan.

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 7 inclusion and 29 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: paused, as of the sponsor's last update on 9 Nov 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 Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

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 participants with treatment-related adverse events as assessed by CTCAE v5.0 (time frame: up to 3 months). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04515953.

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 9 Nov 2023; AzTrials last refreshed its copy on 31 Oct 2026.