A Phase 1 Double-Blind, Double-Dummy, Parallel-Group, Randomized, Positive Control Study Using fMRI to Evaluate the Effect of NKTR-181 on Brain Activity in Healthy, Non-physically Dependent Recreational Opioid Users

The main purpose of this study is to evaluate the effect of NKTR-181 on brain activity in healthy, non-physically dependent recreational opioid users. This study will last about 88 days for each participant.

Start Date22 Oct 2018

Sponsor / Collaborator

Nektar Therapeutics

NCT02367820

/ CompletedPhase 3

A Phase 3 Multicenter, Open-Label, 52-Week Study To Evaluate the Long-Term Safety and Tolerability of NKTR-181 in Subjects With Moderate to Severe Chronic Low Back Pain or Chronic Non-Cancer Pain

The purpose of this 52-week open label study is to determine the long-term safety of a new opioid molecule, NKTR-181, in patients with moderate to severe chronic low back pain or chronic non-cancer pain.

Start Date14 Apr 2015

Sponsor / Collaborator

Nektar Therapeutics

NCT02362672

/ CompletedPhase 3

A Phase 3 Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of NKTR-181 in Opioid-Naive Subjects With Moderate to Severe Chronic Low Back Pain

The purpose of this study is to determine whether a new opioid molecule, NKTR-181, is effective for the relief of moderate to severe chronic low back pain as compared to a placebo.

Start Date11 Mar 2015

Sponsor / Collaborator

Nektar Therapeutics

100 Clinical Results associated with Loxicodegol

100 Translational Medicine associated with Loxicodegol

100 Patents (Medical) associated with Loxicodegol

Literatures (Medical) associated with Loxicodegol

01 Aug 2020·Pain medicine (Malden, Mass.)Q3 · MEDICINE

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain

Q3 · MEDICINE

Article

Author: Siddhanti, Suresh ; Gudin, Jeffrey ; Gimbel, Joseph ; Henningfield, Jack E ; Schnoll, Sidney ; Lu, Lin ; Tagliaferri, Mary ; Doberstein, Stephen K ; Di Fonzo, Carlo ; Rauck, Richard ; Katz, Nathaniel

Abstract:

Objective:

To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.

Design:

Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).

Setting:

Conducted in the United States at multiple sites.

Methods:

SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events.

Results:

Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible “withdrawal” events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo).

Conclusions:

NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.

01 Jul 2020·Pain medicine (Malden, Mass.)Q3 · MEDICINE

Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS)

Q3 · MEDICINE

Article

Author: Gimbel, Joseph ; Argoff, Charles ; Rauck, Richard ; Doberstein, Stephen K ; Tagliaferri, Mary ; Tagliaferri, Margit ; Gudin, Jeffrey ; Siddhanti, Suresh ; Hale, Martin ; Katz, Nathaniel ; Markman, John ; Potts, Jeffrey ; Lu, Lin ; Wild, James ; Agaiby, Eva

Abstract:

Objective:

To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP).

Design:

Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181).

Setting:

Multicenter, long-term clinical research study.

Methods:

NKTR-181 administered at doses of 100–600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF).

Results:

The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events.

Conclusions:

The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.

01 Feb 2020·Pain medicine (Malden, Mass.)Q3 · MEDICINE

Human Abuse Potential of Oral NKTR-181 in Recreational Opioid Users: A Randomized, Double-Blind, Crossover Study

Q3 · MEDICINE

Article

Author: Tagliaferri, Mary ; Kelsh, Debra ; Ziola, Margaret ; Hoch, Ute ; Henningfield, Jack E ; Siddhanti, Suresh ; Doberstein, Stephen K ; Eldon, Michael A ; Lu, Lin ; Ge, Xue ; Zalevsky, Jonathan ; Xie, Sunny ; Jobes, Janet ; Di Fonzo, Carlo J ; Vince, Bradley

Abstract:

Objective:

To evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of oral NKTR-181 (oxycodegol), a novel full mu-opioid receptor agonist, relative to oral oxycodone.

Design:

This double-blind, randomized, single-dose, crossover human abuse potential study was conducted in healthy, adult, non–physically dependent recreational opioid users.

Setting:

Inpatient clinical research site.

Subjects:

Seventy-one subjects randomized (95.7% male, 65.2% African American, mean age = 31.7 years).

Methods:

The primary objective was to compare two therapeutic doses of NKTR-181 (400 and 600 mg) with 40 and 60 mg of oxycodone and a supratherapeutic dose (1200 mg) of NKTR-181 with 60 mg of oxycodone using visual analog scale (VAS) ratings for Drug Liking “at this moment” (Drug Liking). Secondary objectives included VAS ratings for other subjective measures, and central nervous system (CNS) mu-opioid effects were assessed using pupillometry. Each subject received single oral doses of five treatments and matching placebo.

Results:

Compared with 40 and 60 mg of oxycodone, the maximum mean Drug Liking score at 400 and 600 mg NKTR-181 was significantly lower, and the rate of onset and extent of Drug Liking for all NKTR-181 doses in the first two hours postdose were also significantly lower. Delayed attenuated Drug Liking and pupillary miosis response following administration of NKTR-181 vs oxycodone were consistent with slower NKTR-181 CNS entry kinetics and mu-opioid receptor binding. No adverse events were rated as severe, and somnolence and dizziness occurred more frequently when subjects received oxycodone.

Conclusions:

NKTR-181 at oral doses of 400 and 600 mg showed significantly fewer and less severe subjective effects accepted as representative of opioid abuse potential, such as lower peak Drug Liking in recreational opioid users, than 40 and 60 mg of oxycodone.

News (Medical) associated with Loxicodegol

15 Mar 2022

·www.biospace.com

Nektar Left Reassessing After Canceled Melanoma Trials

Smith Collection/Gado/Getty Images After the announcement, Nektar shares dropped 36%, going from $6.47 per share to $4.16. Smith Collection/Gado/Getty Shares of Nektar Therapeutics plunged after a disappointing clinical announcement on Monday. This has prompted the cancellation of two trials and left the company scrambling to find solutions. Nektar and Bristol Myers Squibb announced data from their joint Phase III PIVOT IO-001 study, which was testing Nektar’s immunotherapy drug bempegaldesleukin in combination with BMS’s Opdivo (nivolumab) compared with Opdivo alone to treat unresectable or metastatic melanoma. Unfortunately, the study did not meet its primary endpoints. The results were so dismal that BMS and Nektar not only canceled the PIVOT IO-001 study, they also discontinued their PIVOT-12 study, another Phase III trial where the partners were evaluating the same drugs but for adjuvant melanoma. The announcement is undeniably more difficult for Nektar. BMS had significant revenues of more than $46 billion in 2021, and has a diverse pipeline of products. However, Nektar, which focuses on oncology and immunology diseases, only brought in $101.9 million in revenue last year. After the announcement, Nektar stocks plunged 36%, dropping from $6.47 per share to $4.16. The collaboration with BMS had been a deal worth over $1 billion when the partnership was started in 2018. This was also just the latest in several tough announcements Nektar has had to make. When the company shared its Q4/full-year 2021 financial report just a few weeks ago, Nektar had a year net loss of $523.8 million. Its 2021 revenue was also around $50 million lower than it was in 2020, “due to the recognition of $50.0 million in total milestones from Bristol-Myers Squibb for the initiation of registrational trials of bempegaldesleukin plus Opdivo® in adjuvant melanoma,” the press release noted. Even before this, Nektar was struggling. In May 2019 , the company created a new subsidiary called Inheris Biopharma to commercialize a new opioid product, NKTR-181. In January 2020 , the U.S. Food and Drug Administration voted unanimously 27-0 to not approve the drug. The move dropped shares of Nektar by 14.5% and forced the company to eat $45.2 million in impairment charges. Still, there’s light at the end of the tunnel. Nektar has a few other products that, if successful, could keep the company afloat. NKTR-255 is currently in Phase I/II testing for blood cancers and solid tumors, while NKTR-358 is being tested in patients with lupus, ulcerative colitis and atopic dermatitis in a collaboration with Eli Lilly . Nektar is also partnering with Merck on a late-stage head and neck cancer study . These partnerships have already garnered Nektar around $800 million. If they prove successful, the alliances could help overcome this loss. Nektar also expects to announce top-line data in two more studies with its bempegaldesleukin drug in renal cell carcinoma and bladder cancer within the next few weeks. In the meantime, Nektar is scrambling to prop up the worth of its stocks with a restructure. “Today’s results will obviously mean that we have to make changes to our business operations and the structure of Nektar,” said Nektar CEO Howard Robin. “These changes will be substantial and will be difficult to undertake, but we’re preparing a plan that has a goal of establishing a minimum cash runway through the end of at least 2024 with our existing cash balance.”

Phase 3Financial StatementClinical Trial Failure

06 Jan 2021

·endpts.com

After an up-and-down year, Nektar watches development head Wei Lin walk away as it pursues pipeline rebound

More than any other year in recent memory, 2020 was a rollercoaster of highs and lows —mostly lows. Just ask San Francisco’s Nektar: Despite ditching its opioid program in January and offloading royalties to its two US-marketed meds, the biotech still has hopes for its pipeline to hit a rebound this year. But that rebound won’t happen under the watch of senior VP and head of development Wei Lin, who is stepping down and leaving immunology head Brian Kotzin to step in. Lin is “leaving the company to pursue another opportunity,” Nektar announced on Wednesday. It’s unclear where the Genentech vet is headed next. Nektar poached Lin from Genentech in 2018, where he held roles such as global development leader for cancer immunotherapy and senior medical director over a seven-year stint. The Harvard Medical School grad joined Nektar as senior VP and head of oncology before getting promoted to head of development. “Over the past two years, Wei has played a leadership role in recruiting an experienced clinical development organization and executing a late-stage clinical development strategy for BEMPEG, positioning it for future success,” chief R&D officer Jonathan Zalevsky said in a statement. “I would like to thank him for his contributions to Nektar, and wish him the best in his next opportunity.” With big shoes to fill, Kotzin is stepping up as interim CMO and head of development. The Amgen vet joined Nektar in 2017 and helped lead early development of NKTR-255, the company’s IL-15 receptor agonist currently in two Phase II studies: one for non-Hodgkin’s lymphoma and multiple myeloma in combo with Rituxan or Darzalex, and another in head, neck and colorectal cancer paired with Erbitux. He also spearheaded the Eli Lilly-partnered NKTR-358 program, which is in Phase II for systemic lupus erythematosus and Phase Ib studies for psoriasis and atopic dermatitis. At Amgen, Kotzin served as VP of global clinical development and head of inflammation therapeutics, as well as VP of translational sciences and head of medical sciences/early development. “This is an exciting time for the company with multiple registrational studies underway in a range of tumor types for BEMPEG, a broadening clinical program for NKTR-358 in a number of auto-immune disorders, and an emerging opportunity for NKTR-255 in both hematological malignancies and solid tumors,” Kotzin said. Last month, Nektar sold the royalties to Adynovate and Movantik off to Healthcare Royalty Management for $150 million in cash. The biotech said it would funnel most of the money into two programs: bempegaldesleukin (or NKTR-214) and NKTR-255. Bempegaldesleukin, Nektar’s lead program, is being studied in several Phase III trials in combination with Bristol Myers Squibb’s Opdivo. The CD122-preferential IL-2 agonist is being evaluated in several indications, including metastatic melanoma, renal cell carcinoma and muscle-invasive bladder cancer. That news came just less than a year after Nektar dropped its opioid program, NKTR-181, which was rebuffed by an FDA adcomm last January. The panel voted 27-0 against approving the drug, citing concerns that patients could abuse it and causing their stock $NKTR to fall 15%. On Wednesday morning, the company’s stock was down 0.61%, at $17.97 a share.

ImmunotherapyCollaborate

16 Jan 2020

·www.in-pharmatechnologist.com

FDA unanimously shuts down Nektar’s opioid painkiller

The US FDA’s advisory committee voted 27-0 against recommending approval of oxycodegol, with Nektar deciding to withdraw its application as a result. According to reporting by Reuters , the unanimous decision against the drug resulted from concerns over the potential for abuse of the opioid painkiller, oxycodegol. As well as this, Nektar Therapeutic chose to submit data to US Food and Drug Administration (FDA) based on only one pivot efficacy study rather than two studies. After the rejection, Nektar released a statement outlining its ‘disappointment’ in the decision and that it would withdraw its new drug application (NDA), ending its investment in the development program. With funding cut from the drug candidate, the company noted that it would look to make cost savings of between $75m (€67.2m) and $125m (€112m) in 2020, based on the estimated expense of commercialization and post-approval studies. The share price of Nektar has dropped 16% since the advisory committee’s recommendation was made, despite the positive news the company announcement last week on its extended collaboration agreement with Bristol-Myers Squibb. The decision on oxycodegol comes as the FDA moots various measures to limit the risk of harm posed by opioid painkillers, amid the ongoing opioid epidemic in North America that has resulted in a number of lawsuits targeting manufacturers.

100 Deals associated with Loxicodegol

External Link

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-	-	-	DB14146

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Back Pain	NDA/BLA	United States	Nektar Therapeutics	-
Chronic Pain	Phase 3	United States	Nektar Therapeutics	11 Mar 2015
Low Back Pain	Phase 3	United States	Nektar Therapeutics	11 Mar 2015
Osteoarthritis, Knee	Phase 2	United States	Nektar Therapeutics	01 Jun 2012
Musculoskeletal Pain	Phase 2	United States	Nektar Therapeutics	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01619839 (CTgov)	Phase 2	Chronic Pain \| Osteoarthritis, Knee	296	Placebo (Placebo)	pgxhxmgjbk(gziqiiipgn) = uwxadazhsd jvfcdjutns (jlzzeuzajn, 0.168) View more	-	02 Aug 2021
				NKTR-181 (100 mg NKTR-181)	xzygnurnqk(mzibcyzifo) = bsnprmpucs cysxetrvqh (mmsedcvoij, yffehvimpu - izsllasrye) View more
NCT03802227 (CTgov)	Phase 1	Chronic Pain	8	placebo+oxycodone+NKTR-181 (NKTR-181)	xlflvklanr(zoocuwggeq) = iifgjctstw lusyvjiueg (uodzdboqau, 0.12) View more	-	27 May 2021
				Oxycodone (Oxycodone IR 40 mg)	xlflvklanr(zoocuwggeq) = kaclluqthf lusyvjiueg (uodzdboqau, 0.34) View more
NCT02362672 (SUMMIT-07, CTgov)	Phase 3	Low Back Pain \| Chronic Pain	1,189	NKTR-181 (NKTR-181)	ziuhljtsxx(ygsspallal) = jfjfuishbe kuflrykefp (sogjnwaehr, 0.11) View more	-	16 Sep 2020
				Placebo to match NKTR-181 BID tablets (Placebo)	ziuhljtsxx(ygsspallal) = egkegcdvzj kuflrykefp (sogjnwaehr, 0.11) View more
NCT02362672 (SUMMIT-07, Pubmed) Manual	Phase 3	Low Back Pain	610	NKTR-181	odsarqtwlk(xqxcspkmvt) = pencxnrkdq zidxjgysze (evrnumduru ) View more	Positive	01 Jun 2019
				Placebo	odsarqtwlk(xqxcspkmvt) = vfznpypwgk zidxjgysze (evrnumduru ) View more

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